Objective. To determine the immunogenicity of hepatitis B vaccine in preterm i Methods. One hundred two preterm infants (23 to 36 weeks' gestational age) born to hepatitis B surface antigen-negative mothers were enrolled. Immunization was initiated just before hospital discharge with subsequent doses 1 and 6 months later. Serum specimens were obtained before the administration of each vaccine dose and 3 months after the last dose and were tested for antibody to hepatitis B surface antigen (antiHBs). Results. Eighty-seven infants (85%) completed the study. Ninety percent (n = 78) of infants who completed the study seroconverted (antiHBs greater than or equal to 10 mIU/mL); 10% (n = 9) remained seronegative at study completion. The geometric mean antibody titer to hepatitis B surface antigen for infants who seroconverted was 200 mIU/mL. Nonresponders (NR) differed from responders (R) in birth weight (NR = 2090 g, R = 1560 g) gestational age (NR = 33 weeks, R = 31 weeks), and weight gain before vaccine initiation (NR = 244 g, R = 633 g). There were no differences in weight or age at vaccine initiation, Apgar scores, interval between vaccine doses, or bacterial infections, steroid use, or transfusions before vaccine initiation. Conclusions. Ninety percent of preterm infants responded to hepatitis B vaccine when the first dose of vaccine was delayed until hospital discharge. Nonresponders were more likely to be preterm infants of higher birth weight and higher gestational age, and to have gained less weight before vaccine initiation.