In theory, this could reduce the number of key personnel who would need jabs in any new vaccination programme.
It was previously thought that resistance to the smallpox virus would last only a few years, but researchers at the University of Carolina at Chapel Hill have found otherwise.
They tested blood samples from 13 laboratory workers - some vaccinated within the past five years, and the rest between five and 35 years ago.
The researchers looked for signs of remaining immune response to smallpox virus.
Going strong
They found that, even in people vaccinated decades ago, the response was still potentially strong enough to fight off a new infection.
Dr Jeffrey Frelinger, who led the research, said: "Given the general belief that the vaccinations lasted only seven to 10 years, we were surprised how durable the responses were.
"It is striking that the loss of reactivity over more than 35 years is very low. Resistance is waning but not rapidly. It is still substantial."
At the moment, vaccine is given only to laboratory workers and others who might come into contact with the virus.
However, the US government is currently considering a wider vaccination programme against smallpox in response to bioterror fears.
It is trying to secure larger supplies of vaccine to carry out the campaign.
The research was published in the New England Journal of Medicine.