Purpose: The aim of this study was to compare the hepatitis B surface antibody (HBs Ab) titer 1 month after the 4th dose of hepatitis B vaccine administration on the large and appropriate for gestational age infants. Materials and Methods: This cross-sectional study was conducted on 7-month-old cases (n=132) divided into two groups of 2–4 kg (group 1: appropriate for gestational age, 63 cases) and >4 kg (group 2: large for gestational age, 69 cases), whom were vaccinated with a fourdose schedule of hepatitis B vaccine in 2016, Tehran, Iran. Results: Mean birth weight of the groups was 2.98±0.528 and 4.19±0.190 kg, respectively.Hepatitis B surface antigen and hepatitis B core antibody were negative in all cases. HBs Ab level in group 1 and 2 was 13,701.00±11,744.439 and 8,997.15±2,827.191, respectively (95% confidence interval of difference, -7,607.44 to -1,800.25). There was a significant difference between the two groups in antibody titration and antibody logarithm level (p=0.002, p=0.0001). Conclusion Birth weight may affect the response to the hepatitis B virus vaccine administration.