Kirkpatrick has a longstanding relationship with DreamWorks Animation, where he has contributed as a Writer or story consultant on The Road to El Dorado, Spirit: Stallion of the Cimarron and Madagascar. In May 2006, DreamWorks Animation released Over the Hedge, for which Kirkpatrick co-wrote the screenplay and made his directorial debut, sharing the credit with Tim Johnson. That same year, Kirkpatrick co-wrote the screenplay of the live-action adaptation of E.B. White's classic Charlotte's Web for Paramount Pictures/Walden Media/Nickelodeon Movies. The film starred Dakota Fanning and the voice talents of Julia Roberts, Robert Redford, Steve Buscemi, Oprah Winfrey, John Cleese and many others. He produced and co-wrote, with partner Chris Poche, the original comedy Flakes, which completed filming in New Orleans in January 2005 and stars Zooey Deschanel, Christopher Lloyd and Aaron Stanford. He directed the Eddie Murphy dramedy Imagine That for Paramount Pictures.