Background: Infants of diabetic mothers (IDMs) have a significantly greater risk for perinatal morbidity, mortality, and altered immune response. Aim of work: To assess the immune response of IDMs for hepatitis B virus (HBV) vaccine and to compare them with infants of non-diabetic mothers as a control group.  Patients and Methods: 150 neonates met the inclusion criteria; 100 IDMs and 50 infants' non-diabetic mothers as controls. All neonates who met the inclusion criteria received HBV vaccine during the first 24 hours of age and at 1 and 6 months of age according to the WHO guidelines. Furthermore, hepatitis B surface antigen (HBsAg), hepatitis B virus surface antibodies (anti-HBs), and hepatitis B virus core antibodies (anti-Hbc) were measured at 9, 12, and 24 months of age. Results: IDMs had significantly higher birth weight when compared to infants of the non-diabetic mothers (3.6 ± 0.4 kg and 3.03 ± 0.5 kg, P-value 0.01). There was a significant difference between the response to anti-HBs between case group and control group at 9 months 7±12 mIU/dL versus 20±23 mIU/dL (P-value < 0.0001). However, anti-HBs antibodies levels follow-up at 12 and 24 months showed no significant differences between the case and control groups. Conclusion:At 9 months of age, post HBV vaccination, there was a delayed immune response for HBV vaccine was present in IDM compared to infants of non-diabetic mothers. However, IDM became immune at follow-up at 12 and 24 months of age.