The city said Wednesday that employees will have 10 weeks to get their shots after a vaccine gets final FDA approval.
The three COVID-19 vaccines currently available in the U.S. are being dispensed under emergency authorization by the Food and Drug Administration.
They are expected to receive full approval in several months. San Francisco city employees will then have 10 weeks to get their shots.
City workers who refuse must get a medical or religious exemption, or they could be fired.
San Francisco, a compact city of nearly 900,000 residents, has had some of the strictest pandemic-related restrictions in the country and its vaccination rates are very high.
The vaccination policy for city employees covers a wide range of jobs but it does not include teachers, who are school district employees.
"It's really a decision for the health and safety of our employees and our public that we serve," said Carol Isen, San Francisco director of human resources. "It's about protecting the city as an employer from what we deem to be unacceptable risk."
San Francisco will be the first California city to make vaccinations mandatory.
The Associated Press contributed to this story.
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