OBJECTIVE A randomized, double-blind trial was conducted to compare the efficacy of a high-dose versus standard-dose hepatitis B vaccine in alcoholic patients. METHODS One hundred ten alcoholic patients were randomized to either receive the standard dose (20 micrograms at 0.1, and 6 months) or a high dose (40 micrograms at 0, 1, 2, and 6 months) of recombinant hepatitis B vaccine (Engerix-B). Patients were monitored for relapse of drinking using self-report, serial serum carbohydrate deficient transferrin, and collateral verification. The final titer of antibody to hepatitis B surface antigen (anti-HBs) was obtained 12 months after the first vaccine dose; a seroconversion was defined as a titer greater than 10 mlU/ml. RESULTS One hundred subjects completed the study; 10 of these had clinical or pathological evidence of cirrhosis. Thirty-six out of 48 (75%) of patients administered the high-dose regimen seroconverted compared with 24 of 52 (46%) in the standard dose group (P < 0.005). The mean anti-HBs titer of the high dose group was significantly greater than of the standard dose group (76.4 versus 39.4 mlU/ml, P < 0.01). Logistic regression demonstrated a significant effect on seroconversion for the vaccine dose (P < 0.005) and serum albumin (P = 0.05) but not for the other variables such as race, age, drinking during the study, serum creatinine, arm muscle circumference, and cirrhosis. CONCLUSIONS A high- and accelerated-dose regimen of hepatitis B improves the serological response in alcoholic patients. This regimen (currently recommended for hemodialysis patients) should now also be considered for patients with a history of alcoholism.