In the twenty years since the first film Lloyd Christmas has since been committed to a mental institution. Harry Dunne comes for a visit and reveals that he needs a kidney transplant but also that Lloyd pranked him into thinking that he's in the institution because he's insane. The two go to Harry's parents' home but they cannot provide a kidney because of his adopted status. Looking in twenty years of piled-up mail Harry sees a postcard from his old girlfriend Fraida Felcher who says that she got pregnant but later decided to give up her daughter Fannie for adoption. This leads Lloyd & Harry to go on another road trip to find her.