The store replaces a former Bell Market but some change lovers are not so excited about this change.
The organic grocer came under fire after company CEO John Mackey wrote an op-ed opposing President Barack Obama's campaign to change the health care system.
Since Mackey's views were published by the Wall Street Journal, Bay Area-based organizers have arranged boycotts across California, including a flash mob dance rendition called "Hey Mackey" at the Whole Foods store in Oakland, Calif.
Despite the protest, Whole Foods officials and San Francisco Supervisor and mayoral hopeful Bevan Dufty attended a "bread-breaking" ceremony.
A Facebook group created by disgruntled Whole Foods' shoppers said they planned to protest the opening until 1 p.m. But the Twittersphere, which was working overtime with comments following the flash mob dance, was quiet Wednesday, with most tweets saying there was a large but quiet crowd.