Mpox seemed to fade from the headlines, but the risk did not disappear. In U.S. health records, people who received both recommended vaccine doses had far less mpox than similar unvaccinated people.

Mpox had once been linked mainly to travel, but in 2022 the United States experienced 30,344 cases and 42 deaths—about one-third of the global outbreak. Most U.S. cases occurred among men and transgender people who have sex with men.

The emergency ended, but more than 91,000 human-to-human infections since 2022, rising infections among unvaccinated people, and a resurgence in the Democratic Republic of the Congo all point to a continuing need for preventive vaccination. The concern is not only the past outbreak: a related form of the virus causes more severe illness, so public-health agencies continue to stress preparedness even though it has not been detected in the United States.

To answer whether vaccination worked outside a tightly controlled trial, the study used ordinary U.S. healthcare records to examine protection and safety among vaccinated men who have sex with men and transgender women. That makes the question practical: does the vaccine help people in everyday healthcare, not only under research conditions?

The comparison worked like checking two lines at a store: for each vaccinated person, the study found similar unvaccinated people, matching them by date, age group, region, and insurance type. The unvaccinated comparison group had no record of receiving the vaccine by that matching date, and was matched on calendar date, age group, region, and insurance type.

The central result was a lower risk of mpox among fully vaccinated people than among similar unvaccinated people. Estimated vaccine effectiveness was 89 percent. Among people living with HIV and receiving treatment, the result suggested similar protection, but the uncertainty was wide.

The study could not report a clear difference between people with and without HIV prevention medication in the subgroup without HIV. This filtering reduced a large at-risk population to 163 fully vaccinated patients, each paired with five unvaccinated patients—815 in all.

That careful narrowing matters because the later vaccine comparison rests on groups made similar and complete enough to compare fairly. But here is the catch: protection was lower when the analysis included anyone with any dose, at 64 percent, and it was 70 percent among people with only one dose.

For people older than 50 who were assumed to have had an earlier smallpox vaccine, the study found no evidence of protection from a single dose. The safety result was reassuring within the study’s specified time windows: no safety events occurred among vaccinated people or their matched comparison group after at least one dose.

When the window for heart inflammation was extended to 28 days, one such event was identified among vaccinated people. That finding is important to monitor, but it was a single event in this analysis. There is an important limit to what these records can tell us.

They did not include people’s sexual orientation, gender identity, clinical notes, or other documentation to confirm how participants were classified. If some unvaccinated men did not share the same risk profile as the vaccinated group, mpox could have been undercounted among them, making the vaccine appear more effective than it was.

The researchers used high-risk criteria based on earlier mpox studies, and related studies in Germany collect this information directly from participants to complement these records. Taken together, the results add to evidence that the vaccine works and is safe, while the estimates remain imprecise because the study was small.

The strongest protection appeared among people who received both recommended doses. For someone deciding what to do, the practical message is clear: completing the two-dose course offered the greatest effectiveness seen in this study.

The study found strong protection after two doses, with weaker evidence after only one, and no safety events in the main safety window. For people at risk, completing vaccination matters while protection efforts continue.