The capacity to generate an efficient innate immune response is pivotal for survival. The objective of this study was to investigate innate immune function in relation to long-term survival in the oldest old. We measured ex vivo lipopolysaccharide-induced proinflammatory and antiinflammatory cytokine responses in 562 participants aged 85 years of the general population who were followed for mortality during 10 years. Compared with participants with a high proinflammatory and antiinflammatory response profile, 85 year olds with an overall low proinflammatory and antiinflammatory response had a significant higher mortality risk (hazard ratio: 1.79, 95% confidence interval: 1.29-2.50), whereas participants with a high proinflammatory and low antiinflammatory response had a survival benefit (hazard ratio: 0.74, 95% confidence interval: 0.57-0.97). This benefit was even more pronounced in survivors past 90 years of age (hazard ratio: 0.50, 95% confidence interval: 0.26-0.96). In old age, the capacity to generate an unopposed proinflammatory innate immune response is predictive of long-term survival.