How effective was the smallpox vaccine at preventing smallpox infection?

The smallpox vaccine was highly effective, preventing infection in approximately 95 percent of vaccinated individuals.12

The vaccine works by utilizing the vaccinia virus, which is closely related to the virus that causes smallpox. Because these viruses share many surface antigens, the vaccine stimulates the adaptive immune system to produce antibodies and memory cells that provide cross-immunity against smallpox.1

Following vaccination, immunity typically develops within weeks and is strongest for the first three to five years, though partial protection may persist for decades. Additionally, receiving the vaccine shortly after exposure to the virus can prevent or significantly reduce the severity of the disease. This high level of efficacy, combined with coordinated international public health efforts and strategies like ring vaccination, led to the World Health Organization declaring smallpox officially eradicated in 1980.2341