In Boston from 2010 to 2015, there were 221 gun homicides.

Research suggests that one change could have lowered that number by 40 percent: smaller bullets.

A study last year, published in JAMA Network Open, examined the type of weapon used in every fatal and nonfatal shooting in the city. It found that — regardless of the time of day, the number of wounds or the circumstances of the crime — the size of the bullet affected which gunshot victims lived and which ones died.

At the center of the debate about gun control lies the question of whether the availability of deadly weapons increases the seriousness of crime. Critics of gun control contend it doesn’t. As the popular bumper sticker argues: “Guns don’t kill people. People kill people.” The study set out to test that slogan — and found it wanting.

“The type of weapon matters,” said Philip Cook, an emeritus professor of public policy at Duke University, and one of the study’s co-authors.

If all the shooters in Boston had used the types of guns in circulation with the biggest bullets, the homicide rate could have been 43 percent higher, the researchers calculated recently, even with the same people committing exactly the same crimes.

Over recent decades, the size of bullets fired by the typical handgun has increased. Changes in design have made it easier to fire big bullets from concealable weapons, and manufacturers have marketed more powerful guns as better tools for self-defense. In the 1970s and 1980s, the guns most commonly used in crime tended to be revolvers or small, inexpensive pistols that fired .22-caliber rounds, so-called for their 0.22-inch diameter.

But regulations meant to reduce crimes committed with these cheap, disposable guns, sometimes called “Saturday night specials,” pushed them out of gun stores. And advances in gun technology caused a new generation of weapons to hit the market — and eventually the streets. The newer guns, which started to become common in the 1990s, were semi-automatic. They could fire multiple rounds more quickly, and tended to be able to store more bullets in their magazines, meaning they required less reloading in long shootouts.

And instead of buying guns that fired smaller bullets, people started purchasing ones that fired rounds that were 9 millimeters wide, about 0.35 inches, then 0.40 and 0.45 inches.

Guns that fire big bullets used to also be big. But improvements in technology have meant that large-caliber weapons are now available as pistols that can be more easily carried and hidden.

These advances, intended for the legal self-defense market, have spread to the criminal one, too. Although data about the guns owned and used by criminals is imperfect, evidence suggests that criminals’ buying preferences are not substantially different from that of the general public. A recent study of guns used by criminal gangs, also in the Boston area, found that gang members paid the most for large-caliber semi-automatic pistols, which they often bought secondhand at prices much higher than those paid by legal purchasers in gun stores. Police seizures of guns in other cities, including Chicago, also show a growing share of large-caliber handguns.

“In general, the criminals who are using guns in crime do want the higher-caliber, more lethal weapons, and want the newest and sexiest,” said Roseanna Ander, the founding executive director of the Crime Lab at the University of Chicago. “But there is a big markup, and they sometimes can’t get them.”

A foundational statistical study in 1972 looked at detailed crime records in Chicago and first documented a relationship between weapon type and outcome. Franklin Zimring, a professor of law at the University of California, Berkeley, said he had been surprised to see so much similarity in the circumstances between fatal and nonfatal shootings. What made the difference, he said, appeared to be some combination of luck, aim and the weapon involved.

Mr. Zimring called that paper “The Medium Is the Message,” but said he had been urged to title it “The Bigger the Bullet, the Bigger the Hole.” In the decades since, little has been done to replicate its results. The police don’t always collect information about the caliber involved in shootings. Detailed data about all the particulars of nonfatal shootings is particularly rare.

But when Anthony Braga, the director of the school of criminology and criminal justice at Northeastern University, and Mr. Cook learned that Boston’s Police Department was collecting information about caliber as part of an effort to improve its homicide clearance rate, they decided to retest that earlier thesis. It took five years of shootings for the researchers to collect enough data to draw firm conclusions.

Bigger rounds can have their drawbacks for shooters, particularly when loaded into compact handguns. Because the bigger ammunition tends to fire with more explosive power, the .40- and .45-caliber handguns that some Boston criminals were using can have strong recoil that can make them hard to handle or to aim subsequent shots. The trade-off between caliber and aim is, in part, why the F.B.I. and many police departments carry 9-millimeter guns rather than larger alternatives. But accuracy seemed a less important consideration for the Boston criminals in the data the researchers examined. Unlike police shootings, most of the shootings in the sample involved a single bullet wound.

“Their aim is terrible, fortunately,” Mr. Cook said. “A lot of these cases are drive-bys or cases where you just wouldn’t expect that there’s any sharpshooting going on.”

If people are determined to kill someone, will they find a way? Critics of the study’s conclusion contend that the choice of gun itself can be an expression of a criminal’s intent.

“As far as I know, everyone in the field believes bigger-caliber handguns are more lethal than smaller-caliber handguns — it’s a nonissue,” said Gary Kleck, a professor emeritus of criminology at Florida State University, in an email. But he said the study failed to take into consideration that a larger gun might signal a more determined killer. “The authors’ implied claim that lethality of the shooter’s intent has no effect on victim death is bizarre.”

There are no serious current proposals to regulate or limit the sale of handguns by caliber size. A recent anonymous survey of gun researchers by the nonpartisan RAND Corporation found that the field remains divided on the question of how much weapons matter in crime

It’s true that the era of larger-caliber handguns has also been an era of declining violent crime. Homicides in most major American cities peaked in the early 1990s, just before larger-caliber pistols became common. The homicide rate has fallen nearly by half since then. But the research about weapon caliber suggests it could have dropped by even more.

“Would we have done still better with smaller guns and if we had stuck with Saturday night specials?” Mr. Cook said. “The answer is sure, absolutely. I think the shift towards more reliable and more high-powered guns has been contributing to the deadliness of gun violence.”