- Upon learning that their mother has been lying to them for years about their allegedly deceased father, fraternal twin brothers hit the road to search for him.
- Kyle and Peter Reynolds are fraternal twins who were raised by their mother, Helen, as their father died before they were born. Kyle has a pregnant girlfriend, Kaylani, and is wealthy from royalties for his image on BBQ sauce labels. Peter is divorced with a teenage son who resents him. Shortly after Helen's wedding, Peter recognizes an actor on "Law and Order: SVU" from photos of his supposed father, and confronts Helen. Helen explains that she had been promiscuous at the time of their conception and did not want their father involved. When they keep pressing, Helen reveals that their father is Terry Bradshaw. The brothers fly to Florida to meet Bradshaw at a signing event. Bradshaw is excited to have them as sons. As Bradshaw recounts stories with former teammate Rod Hamilton, the brothers realize that Bradshaw had been in Australia at the time of their conception, and thus isn't their father..
- In middle age, fraternal twin brothers Peter and Kyle Reynolds could not be more different. Divorced Peter is uptight by nature. He realizes that he is unhappy with his life: he hasn't been with anyone since his divorce three years ago--from his college sweetheart and the only woman he had even been with, Katherine; he and his teenage son Ethan have never gotten along; he doesn't really like being a proctologist and had only become one to honor the supposed father who had died of colon cancer before he and Kyle were born. Ex-surfer Kyle is a free spirit living in Hawai'i, off the lucrative royalties from his image being used for a commercial Hawaiian barbecue sauce in the latest item in what seems to be his charmed life. He has never been married and is currently in a serious relationship with equally free spirit Kaylani. At the wedding of their mother Helen--her first since their father's passing, Peter and Kyle discover by chance that the stories Helen had told them about their father for all these years were all lies: she doesn't actually know who their father is. Peter is arguably more devastated by this news as it was on what he based his life. With what little Helen tells them, Peter and Kyle go on a quest to find their father: a journey of discovery about the list of "candidates", but also about their mother, their twin relationship, and themselves.—Huggo
- Peter Reynolds (Ed Helms) is a physician who spends his days performing rectal exams on his patients. He's also divorced and his son Ethan (Zachary Haven) has little respect for him.
Peter takes Ethan to attend the wedding of his mother Helen Baxter (Glenn Close). Peter's twin brother Kyle (Owen Wilson) is there with his pregnant girlfriend Kaylani (Jessica Gomes). Peter resents Kyle for living frivolously due to receiving royalties for including his image on bottles of hot sauce.
After the ceremony, Peter is watching an episode of the TV show "Law and Order" when he notices one of the actors looks familiar to him. After being told that their father died of colon cancer (which is what drove Peter to pick the job he has now), he suspects that his father may actually still be alive because the actor on the show has a birthmark similar to what Helen told the guys their dad had. Helen eventually admits that she lied about their father because she felt that their real dad wasn't fit enough to raise them. After Peter angrily presses Helen for more information, she relents and says their dad could be Terry Bradshaw. Peter gets excited because he idolized Terry growing up. Knowing he lives in Miami, Peter and Kyle make a trip to go find him.
On the plane ride to Miami, Kyle tries to play matchmaker for Peter with a stewardess. Peter is hesitant despite not being in a relationship with anyone since his ex-wife. Kyle wants to make it a side goal on their trip for Peter to get laid.
The brothers go to a stadium where Terry is having a meet-and-greet. Peter takes out a picture of Helen and shows it to Terry, leading him to reminisce fondly (and sexually) about Helen, which causes him to believe he really is Peter and Kyle's father. Terry invites them to his house and later plays catch on the beach with Peter. When Kyle is thrown the ball, he runs to catch but gets knocked on his ass by Terry's friend Rod Hamilton (Ving Rhames). He also has pleasant, steamy memories of Helen. When Peter mentions a trip that Helen supposedly went on with Terry to Australia around the time of the guys' conception, Terry mentions that she never went with her, so he couldn't be their father. Terry and Rod mention a man that Helen later dated named Roland Hunt (J.K. Simmons), whom Rod thinks Peter resembles.
Peter and Kyle head off to find Roland. While outside his house, Roland approaches them with a gun, thinking they are burglars. He drops it when the guys mention Helen. Roland invites them inside with his wife (June Squibb). When the guys mention they might be his sons, Roland goes into the kitchen and goes nuts at the thought of being their dad. After calming down, Roland goes to the guys and asks them for help with something.
The three go to the home of a wealthy neighbor because Roland wants to steal his Ferrari. The man and his wife go outside to see this happening, and Roland runs off to leave Peter and Kyle. However, Roland has a change of heart and goes back for them, only to get hit when the guys actually try to make off with the Ferrari.
The guys take Roland to the hospital. The doctors tell them that after a blood transfusion, they found that Roland's blood type does not match the guys, meaning he can't be their father. The guys go into Roland's room to apologize for what happened. He tells them he realized he couldn't be their father because around the time that they were conceived, he was in jail after another one of Helen's boyfriends, "Sparkly P", ratted Roland out for possessing cocaine. The guys figure Sparkly P could be their real dad.
While driving to find the man, the guys encounter a hitchhiker (Katt Williams). They pick him up and head to the man's destination, only for their car to get stranded in the middle of nowhere at night. Peter and Kyle start to argue, with Peter resenting Kyle for why he thinks his life sucks. Moments later, a train starts to approach, and they are sitting on the train tracks. Peter gets the hitchhiker out, but Kyle is stuck in the car. The train collides with the car, and Peter fears that Kyle is dead until he emerges from the distance and runs to Peter. They hug until Kyle punches Peter in the face for leaving him there.
The police and medics arrive to tend to the guys. Kyle mentions to Peter that he has been dropped by the hot sauce company and is being replaced by a dog. After the cops clear the guys to go home, Peter mentions Sparkly P, and the cops recognize that name because Sparkly P, better known as Patrick O'Callaghan, was a former respected cop. One of the cops gives the guys his last known address for them to find him.
The guys stop at a hotel for the night. Peter goes to the bar and sees a crying woman named Sarah (Katie Aselton). He approaches her and starts up a conversation. She finds him charming, and the two later go to her room to have sex.
In the morning, the guys head over to the O'Callaghan house to see a party going on. However, they soon find out it's a wake, as Patrick is dead. The guys are disappointed to find out that their potential dad is gone. Patrick's daughter goes up to make a speech, and Peter is mortified to see that it's Sarah, leading him to believe he slept with his sister. He runs out of the house, accidentally spilling a drink on one of Patrick's son's girlfriends. The sons start to fight Peter and Kyle outside until Patrick's twin brother Kevin (Jack McGee) comes out to break things up. The guys mention they are Helen's sons, and Kevin sends everyone else inside to sort things out. After sitting Peter, Kyle, and Patrick's children together, Kevin says that Patrick could not have been the guys' father, because he and Helen never had sex. They were to marry, and Patrick wanted to consummate afterwards, but she ran off with the man she truly loved, Walter Tinkler (Christopher Walken).
Peter and Kyle go to find Walter, who is a doctor and actually lives closer to their home. When Walter sees them and learns whose kids they are, he tries to run for it until Kyle hits him with a tranquilizer dart.
Helen arrives after hearing what's been happening. She finally confesses the truth to Peter and Kyle - she was never their biological mother. The guys' true mother was a young woman who Helen met when she worked at a clinic when the woman was six months pregnant with the boys. She went into labor early, and Helen managed to help her deliver Peter and Kyle, but their mother did not survive. Helen started the adoption process, and while Walter was in love with her, he couldn't uproot his life for someone else's babies. Although Kyle feels frustrated at this revelation at first, Peter comforts him with the fact that they were still raised by a great lady like Helen. The guys then hug Helen.
Peter and Kyle part ways at the airport more amicably than they have been before.
One year later, Peter is in Hawaii with Ethan, who now respects his dad more, and Sarah, whom Peter is dating. Kyle and Helen are also there with Kyle's twin children. It is also revealed that Peter and Kyle have launched their own app for users to receive helpful messages from the universe, which are recorded by none other than the hitchhiker.
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