It is taking effect first in jurisdictions that didn't challenge the requirement in court. Those include some of the biggest states, with some of the largest populations of senior citizens, among them: California, Florida, New York and Pennsylvania.
"There absolutely have been employee resignations because of vaccination requirements," said Catherine Barbieri, a Philadelphia attorney who represents healthcare providers. But "I think it's relatively small."
At Wilson Medical Center in rural Neodesha, Kansas, three of the roughly 180 employees are quitting, and several others have sought exemptions from the vaccine mandate, said hospital spokeswoman Janice Reese.
"We are very fortunate that that is all we are losing," she said, noting that the hospital was not in favor of the mandate. "We didn't feel like it was our place to actually try to tell a person what they had to do."
Reese said the vaccine requirement could also make it more difficult for the hospital to fill vacancies.
In Florida, medical centers find themselves caught between dueling federal and state vaccination policies. They could lose federal funding for not adhering to the Biden administration mandate, but could get hit with fines for running afoul of state law.
Gov. Ron DeSantis, a Republican who has waged a legal campaign against coronavirus mandates, last year signed legislation that forces businesses with vaccine requirements to let workers opt out for medical reasons, religious beliefs, immunity from a previous infection, regular testing or an agreement to wear protective gear. Businesses that fail to comply can be fined $10,000 to $50,000 per violation.
Asked if the state would pursue fines against hospitals that enforce the federal mandate, a spokeswoman for the Florida attorney general said all employee complaints "will be thoroughly reviewed by our office."
Some states already have their own vaccine requirements for healthcare workers. In California, for example, they have been required to be fully vaccinated since Sept. 30 and must get a booster b y Feb. 1.
The federal mandate is "better late than never," said Sal Rosselli, president of the National Union of Healthcare Workers, which represents about 15,000 people in California. "But if it happened sooner, we wouldn't have gone through the surge, and a lot more people would be alive today."
The government said it will begin enforcing the first-dose vaccine requirement Feb. 14 in two dozen other states where injunctions were lifted when the U.S. Supreme Court upheld the mandate two weeks ago. The requirement will kick in on Feb. 22 in Texas, which had filed suit separately.
In Missouri, one nursing home served notice this week that it intends to take advantage of a state rule that allows facilities to close for up to two years if they are short-staffed because of the vaccine requirement. The state health department would not identify the nursing home, saying it is still notifying families and arranging transfer plans.
"Obviously we are proponents of vaccines," said department spokeswoman Lisa Cox. But "throughout all of this, we knew that mandating it would be a negative impact really on our healthcare system ... just because of crippling staffing levels."
The Centers for Medicare & Medicaid Services ultimately could cut off funding to places that fail to comply with the mandate. But it plans to begin enforcement with encouragement rather than a heavy hand.
CMS guidance documents indicate it will grant leniency to places that have at least 80% compliance and an improvement plan in place, and it will seek to prod others.
"The overarching goal is to get providers over that finish line and not be cutting off federal dollars," said MaryBeth Musumeci, a Medicaid expert with the nonpartisan Kaiser Family Foundation.
The states affected on Thursday are: California, Colorado, Connecticut, Delaware, Florida, Hawaii, Illinois, Maine, Maryland, Massachusetts, Michigan, Minnesota, Nevada, New Jersey, New Mexico, New York, North Carolina, Oregon, Pennsylvania, Rhode Island, Tennessee, Vermont, Virginia, Washington and Wisconsin, along with the District of Columbia and U.S. territories.