In 2009, “The Hangover” grossed $467 million worldwide, catapulting Zach Galifianakis from eccentric sidekick to eccentric sidekick on a marquee level. His work this year has demonstrated the “Hangover” effect: A sequel earned $581 million; buddy comedy “Due Date,” from “Hangover” helmer Todd Phillips, netted $211 million; and the recently released “Puss in Boots” features Galifianakis voicing a cracked version of Humpty Dumpty. Despite finding a Hollywood niche that works, he remains devoted to such smaller projects as HBO’s “Bored to Death.” “It’s a show that seems a bit unfamiliar,” he says. “It looks different. It smells different. It sounds different from what is on TV at the moment.”

“Different” is important to Galifianakis. He started as a standup, mining macabre one-liners, piano playing and super-short impressions — like a can of Altoids. (Sadly, he notes, “I have seen what is out there now, and I am rusty. At best.”) He’s grateful for “The Hangover,” but unwilling to let its success define his career. “The temptation is to keep going into that ‘same’ realm — Hollywood has a dangling carrot over entertainers to keep doing the same thing,” he says. “I try to stay away from that very thing.”