A powerful Massachusetts nurses union is again pushing for mandated staffing levels, setting the stage for a contentious and expensive fight with hospitals for the support of voters in November.

A ballot initiative backed by the Massachusetts Nurses Association would set strict limits on the number of patients assigned to a nurse at one time, for all hospital units in the state. Union nurses say they are often overburdened, leaving them unable to give the best possible care and increasing the risk of patient falls, infections, and other complications.

“Every time you add another patient to your workload, you miss things,’’ said Marlena Pellegrino, a union official and a nurse at Saint Vincent Hospital in Worcester for the past 31 years. “Things fall through the cracks.’’

The hospital industry is fighting back, with executives saying the measure is rigid, unreasonable, and would do nothing to improve patient care. Health care executives say the cost to hire additional nurses would force some hospitals to turn away patients, shut down services, or perhaps close entirely.

Steve Walsh, president of the Massachusetts Health & Hospital Association, an industry group, said hospitals collectively would have to hire at least 4,500 new nurses to comply with the ballot measure, at a cost of $880 million per year that would be shared by consumers.

“It’s going to drive up the cost of care . . . right into your premium,’’ Walsh said.

But union representatives challenged the hospital industry’s cost estimates, and said there is a real need for the ballot initiative.

“Hospitals can afford this, there is no question about that,’’ said Kate Norton, a vice president at the consulting firm CK Strategies, which is running the union’s ballot campaign.

Opponents of the ballot question have filed a legal challenge, which is pending in the state’s Supreme Judicial Court.

Staffing levels have long been a source of strife between hospital administrators and unionized nurses. The union has been pushing to legislate nurse-to-patient ratios for more than two decades, and disagreements about staffing have contributed to nurses going on strike, including the walkout by 1,200 nurses at Tufts Medical Center last summer.

Staffing mandates help protect the ranks of union workers. But hospital executives have resisted such measures, preferring the flexibility to staff departments as they choose.

The nurses association proposed putting staffing ratios on the ballot in 2014, but it dropped that campaign after the Legislature approved a compromise that set patient limits in intensive care units, where the sickest patients are. (ICU nurses may be assigned up to two patients.)

This year, lawmakers seem unlikely to intervene. Union representatives insist they will take the issue to voters in November.

The union’s determination is rattling hospital executives.

Dr. Bruce Auerbach, president of Sturdy Memorial Hospital in Attleboro, said that his community hospital would have to increase its nursing staff by 25 percent — about 63 full-time positions — at an annual cost of more than $5 million to comply with the proposed rules.

“If this were to go into place, Sturdy would have to take a serious look at every single program we run in the institution, and make some serious decisions about whether or not we are able financially to continue those programs,’’ he said.

The nurses union has launched a group, called the Committee to Ensure Safe Patient Care, to push its ballot question. The committee has support from several other labor unions, and it had spent more than $1 million before the end of 2017 as it collected tens of thousands of signatures to submit the question for the statewide ballot.

One more round of signatures is needed by July to get the measure on the November ballot.

Hospitals, which have the support of some business groups and nursing organizations, have formed their own coalition to oppose the measure. The Coalition to Protect Patient Safety raised $10,000 by the end of 2017 and is expected to raise and spend millions more this year.

The ballot measure sets different staffing ratios for different parts of the hospital. For typical medical and surgical patients, one nurse would be responsible for no more than four patients at a time, according to the initiative. For sicker patients, the limits are more strict.

Many hospitals already staff nurses at about the levels detailed in the ballot question, but they add or reduce nurses depending on needs. Hospitals tend to staff fewer workers at night, when more patients are sleeping.

The ballot question would forbid hospitals from meeting the costs of the nurse staffing regulations by cutting other health care workers and impose penalties of up to $25,000 for each violation.

Amanda Stefancyk Oberlies, chief executive of the Organization of Nurse Leaders, which represents nursing executives, said the ballot measure would strip power from hospitals to make staffing decisions based on the severity of their patients’ conditions, the experience level of their nurses, and the number of other workers — such as pharmacists and physical therapists — who are available to help patients.

“Making a patient assignment is so complex,’’ Oberlies said. “Every patient is different. Every nurse is different. So it’s not the best policy to just prescribe arbitrary numbers.’’

Studies from several researchers, including Judith Shindul-Rothschild, a professor at Boston College’s nursing school, have shown links between a higher level of nurse staffing and improved pain management, wait times, patient satisfaction, and other measures.

Nurse staffing is “the most consistent factor we’ve studied’’ that is tied to better patient outcomes, said Shindul-Rothschild, who favors setting patient limits.

But others say the research doesn’t prove that mandated ratios are the right strategy.

“These are associations — this isn’t cause and effect,’’ said Peter Buerhaus, a professor at Montana State University who studies the nursing workforce.

California is the only state with mandated nurse-to-patient ratios.

“Most states that have looked at this have backed out of all-out regulation,’’ Buerhaus said.

Priyanka Dayal McCluskey can be reached at priyanka.mccluskey@globe.com. Follow her on Twitter @priyanka_dayal.