Hepatitis B vaccine is a key tool for the prevention of hepatitis B infection. Age-associated changes in immune function may contribute to decreased vaccine efficacy in older individuals, although research related to this topic has yielded contradictory findings. We performed a meta-analysis of 24 published trials and studies that evaluated the association of age with response to hepatitis B vaccine, using a random-effects model. Pooling of study results suggested a significantly increased risk of nonresponse to hepatitis B vaccine among older individuals (relative risk [RR], 1.76; 95% confidence interval [CI], 1.48-2.10). An elevated risk of nonresponse persisted even after exclusion of poor-quality studies (RR, 1.63; 95% CI, 1.23-2.15) and adjustment for publication bias (RR, 1.52; 95% CI, 1.26-1.83), and it was present even when " older" individuals were defined as being as young as 30 years. These findings have important implications for individuals at risk for hepatitis B infection, including health care workers and travelers.