Aim: To determine the influence of gestation and weight on the development of protective anti‐HB levels and geometric mean titres after three doses of HBV vaccine and to ascertain the need for a fourth dose in low birthweight infants. Methods: Hepatitis B vaccine (Enivac HB, Panacea Biotec Ltd., India) was given to 82 preterm (PT) and 60 term intrauterine growth‐retarded (T‐IUGR) infants at birth and at 6, 10 and 14 wk of life. Results: Protective anti‐HB levels (>10 mIU/ml) were reached in 86.6% (71/82) of PT infants and 96.7% (58/60) of T‐IUGR infants after three doses of HBV vaccine (p= 0.044). The odds of having a protective response after the third dose of HBV vaccine was 1.25 (95% CI 1.02–1.53) with every one‐week increase in gestation (p= 0.032). Birthweight was not associated with the development of a protective immune response. After the third dose, only 66.7% (8/12) of the PT infants whose mothers had anti‐HB antibodies, developed protective anti‐HB levels compared with 90% (63/70) of those with no maternal antibodies (p= 0.028). In PT infants after the fourth dose, there was a significant increase in the proportion of infants with protective antibody levels (8.6%, 95% CI 0.6–16.6%) among those with no maternal antibodies and 12.2% overall (95% CI 6.0–21.3) (p= 0.031 to 0.002) over that reached with the third dose. Administration of the fourth dose to T‐IUGR infants did not confer such a benefit. Conclusion: In HBV‐endemic areas, PT infants, irrespective of their birthweights, may benefit from an additional dose of hepatitis B vaccine in a schedule starting at birth. This approach will prevent vertical transmission and bring their immune response up to par with term infants. Term intrauterine growth‐retarded infants should be vaccinated as per the schedule recommended for normal term infants. However, studies in other settings with different vaccine formulations and a longer follow‐up period will be required before this strategy can be practised more widely.