To compare seroprotection achieved by intradermal versus intramuscular hepatitis B vaccine, we conducted a systematic review of observational studies and a meta-analysis of randomized trials. Meta-analysis of data from 757 adults demonstrated that intradermal hepatitis B vaccination was slightly (14%) less likely to achieve seroprotection than intramuscular vaccination (risk ratio(pooled) 0.86; 95% confidence interval: 0.77-0.95). Diverse study methodologies detracted from our ability to synthesize data from these studies; standardized approaches would enhance comparability of future studies. Seroprotection from intradermal vaccination was higher among females and children, suggesting that these populations may be most appropriate for future intradermal vaccine development efforts.