Life-history theory predicts a tradeoff between reproductive effort and lifespan. It has been suggested that this tradeoff is a result of reproductive costs accelerating senescence of the immune system, leading to earlier death. Longevity costs of reproduction are suggested for some human populations, but whether high reproductive effort leads to impaired immune function is unknown. We examined how reproductive effort affected postreproductive survival and the probability of dying of an infectious disease in women born in preindustrial Finland between 1702 and 1859. We found that mothers delivering twins had reduced postreproductive survival after age 65. This effect arose because mothers of twins had a higher probability of succumbing to an infectious disease (mainly tuberculosis) than mothers delivering singletons. The risk among mothers of twins of dying of an infectious disease was further elevated if mothers had started reproducing early. In contrast, neither female postreproductive survival nor the risk of succumbing to an infectious disease was influenced by the total number of offspring produced. Our results provide evidence of a long-term survival cost of twinning in humans and indicate that the mechanism mediating this cost might have been accelerated immunosenescence.