Perhaps it was the March weather that had Gus Van Sant irritated; or the hours he’d spent fielding questions from the media since arriving in Columbus to participate in the Wexner Center retrospective of his work.

Whatever the case, it took more than a little prodding to get the 50-year-old filmmaker to open up about his new film, “Gerry,” which some critics have likened to an endurance test for moviegoers.

“I don’t think it has limited commercial appeal,” he said, obviously displeased with the assumption “Gerry” is too obscure to connect with audiences.

“We really didn’t know how commercial ‘Good Will Hunting’ would be when we were making it. So when we made ‘Gerry,’ we very well could have ended up with ‘Good Will Hunting 2.’ “

The new film, starring Matt Damon and Casey Affleck as best friends who get lost in the desert and spend days trying to retrace their steps, is decidedly not a sequel to “Good Will Hunting,” the Oscar-winning hit about a troubled math prodigy (Damon) that charmed audiences to the tune of $150 million in 1997.

Using action and dialogue sparingly, “Gerry”– which was introduced by Van Sant at a Wexner screening Thursday — might sooner draw comparisons to Samuel Beckett’s “Waiting for Godot.”

The film represents yet another digression in a career that has been as unpredictable as any of our time. A quick glimpse at the program handed out during the retrospective shows the prolific ease with which Van Sant has jumped from arid satire to heartfelt drama, from independent cinema to big-budget Hollywood movies.

“I got lucky,” Van Sant said, recounting his success at working both inside and outside the studio system.

The director is quick to dispel assumptions about the freedom associated with low-budget filmmaking, insisting that independent companies can be as overbearing as major studios.

“The experience of making an independent film is similar to doing a Hollywood film,” he said. “I guess the difference is (independent companies) might accept a script you wouldn’t think of as a ‘Hollywood script.’ They’re likely to be more interested in doing a ‘Drugstore Cowboy’ or something like that.”

“Drugstore Cowboy,” Van Sant’s 1989 road movie about the desperate lives of junkies who rob pharmacies to support their habit, was as important in the establishment of American independent cinema as any film that had come before. It put Van Sant’s name on the map.

He quickly followed up the effort with a succession of offbeat projects: “My Own Private Idaho,” about gay street hustlers, “Even Cowgirls Get the Blues,” adapted from a Tom Robbins novel, and “To Die For,” a media-age satire starring Nicole Kidman as a television weathergirl who will stop at nothing to be famous.

Asked to name the films that most greatly influence his work, he said: “I don’t look at as many older films for inspiration nowadays. But I used to watch certain movies back when I was preparing my first films. I watched ‘Last Tango in Paris,’ ‘Psycho,’ ‘Dr. Strangelove,’ ‘Citizen Kane’ — the American classics.”

The influence of that second film may have caused Van Sant more trouble than it was worth. After the success of “Good Will Hunting,” one of the most profitable films of the late 1990s, the world of Hollywood filmmaking beckoned, and he used his newfound commercial status to finance a shot-for-shot color remake of “Psycho,” which played to devastating reviews and indifferent audience response.

Two years later, the director redeemed his commercial reputation with the upbeat “Finding Forrester,” but many questioned whether he had abandoned the indie sensibility that made him famous.

With the release of his new film, Van Sant’s career seems in the midst of yet another transition. Following the ups-and-downs of his “commercial period,” the director was candid about his efforts to reevaluate his approach to film.

“I’m trying to unlearn a lot of preconceptions,” he said. “Preconceptions like when you assume, because you’ve watched a lot of films, that you have to tell a story through dialogue. What I’m trying to do now is have the dialogue just be about dialogue. To have it not be about guiding the story, but relating it to the way we live.”