A double-blind, randomized controlled trial over 5 years compared the safety, immunogenicity, and efficacy of cold-adapted and inactivated influenza A vaccines in 5210 normal subjects. Both vaccines were well tolerated. Inactivated vaccine significantly increased hemagglutination inhibition antibody titers. Significant titer rises were also noted after cold-adapted vaccine but of lesser magnitude than with inactivated vaccine. The efficacyof inactivated vaccine in preventing culture-positive influenza was 76% (95% confidence interval [CI], 58%–87%) for HINI disease and 74% (95% CI, 52%–86%) for H3N2; for cold-adapted vaccine, 85% (95% CI, 70%–92%) and 58% (95% CI, 29%–75%), respectively. The efficacy of inactivated vaccine in preventing a four-fold rise in antibody titer over the influenza season was 69% (95% CI, 61%–76%) for H1N1 and 73% (95% CI, 65%–79%) for H3N2; for cold-adapted vaccine, 54% (95% CI, 44%–62%) and 32% (95% CI, 17%–44%), respectively. Cold-adapted and inactivated influenza vaccines are safe and effective for preventing influenza A disease.