Objective: The present study aimed to determine the significance of maternal hepatitis B viral load and HBeAg status in neonatal immunoprophylaxis failure. Material and Methods: The present study was designed as a retrospective case study (n= 52). Children who were followed up due to immunoprophylaxis failure and the development of chronic hepatitis B infection were included in the case group (n= 16). The control group (n= 36) included children with successful immunoprophylaxis. The viral load (high/low) and HBeAg status (positive/negative) of the mothers of both groups of the children were compared. Furthermore, possible factors that could lead to immunoprophylaxis failure (gestational age, birth weight, delivery method, premature membrane rupture, breastfeeding length) were also analyzed in both groups. Results: A moderate positive correlation (φ= 0.549, p< 0.001) was determined between the viral loads and a strong positive correlation (φ= 0.758, p< 0.001) was determined between HBeAg statuses. However, gestational age, birth weight, delivery methods, history of premature rupture of membranes, and breastfeeding duration were similar in both groups. Conclusion: Neonatal immunoprophylaxis failure risk was statistically higher if the mother is HBeAg positive and/or has a high viral load (≥2000 IU/mL).