The superimposed occurrence of acute hepatitis A (HAV) on chronic liver disease (CLD) is associated with increased morbidity and mortality. This study evaluated the efficacy of HAV vaccine in 475 subjects with chronic liver disease and controls. Two doses of HAV vaccine (HAVV) 1440 EU was administered 6 months apart. Over 94% of all vaccinees seroconverted after the full course but CLD patients with viral hepatitis had 73% seroconversion after one dose compared to healthy controls (93%) or nonviral diseases (83%). This study also compared safety of HAVV with hepatitis B (HBV) vaccine in patients with chronic hepatitis C and found that HAVV elicited fewer local injection site effects. Overall, HAVV was well tolerated and induced a satisfactory immune response in CLD patients.