Mel Gibson was supposed to play the tattoo artist, but the idea was later dropped following protests from the cast and crew. He was replaced by Liam Neeson. Director Todd Phillips later wanted to reshoot Neeson's scene, but Neeson was unavailable to return, as he was filming Wrath of the Titans. The scene was subsequently reshot with Nick Cassavetes in the role.
Ed Helms (Stu) was severely sick from food poisoning when dancing in the street with no shirt on. After each take Helms would curl into a fetal position until it was time to film again.
When filming the scene where Stu discovers the tattoo on his face, Bradley Cooper genuinely broke into laughter and the director Todd Phillips decided to keep that take in the film.
The three Billy Joel references in the movie (a "Glass Houses" poster in Alan's room; the song "The Downeaster 'Alexa'" on the soundtrack, and the parody of "Allentown" sung by Ed Helms) stemmed from Todd Phillips's desire to decorate Alan's bedroom with the poster, feeling that Alan would strongly identify with it.
The character Teddy's achievements closely resemble that of Ken Jeong who took part in the High IQ team, played violin in the orchestra, was elected to student council and graduated at 16.
The trivia item below may give away important plot points.
Mike Tyson is said to have taken singing lessons for his role as the singer for Stu's wedding, performing an off-key rendition of "One Night in Bangkok".