Rationale: Pentavalent vaccines offer significant public health benefits by protecting against five major diseases with a single injection. However, concerns have been raised in various studies regarding potential associations between combined vaccines and conditions such as autism, febrile seizures, sudden unexpected death in infancy, demyelinating disorders, and neurodevelopmental disorders. Objective: This study aimed to evaluate the safety of pentavalent vaccines administered to infants aged between 6 and 14 weeks. Methods: A total of 423 infants, all aged 6 weeks and receiving their first pentavalent vaccine at selected healthcare facilities, were recruited for the study after obtaining informed consent from their mothers or caregivers. The infants were administered three doses of the vaccine at 6, 10, and 14 weeks. Mothers and caregivers were provided with diaries and thermometers to monitor and record any Adverse Events Following Immunization (AEFI) observed in their babies after each vaccine dose. Follow-up was conducted through telephone calls to ensure accurate monitoring and recording of any identified events. Results: The study identified various AEFIs in the infants following their routine immunizations. These included pain at the injection site, fever, swelling at the injection site, vomiting, refusal to feed, excessive crying, coughing, rash, stooling, restlessness, and severe local reactions. Fever was the most commonly reported systemic AEFI, with incidence rates decreasing from 66.98% after the first dose to 55.37% after the third dose. Pain and swelling at the injection site were the most frequently reported local AEFIs, with their incidence also decreasing from the first to the third doses. No statistically significant differences were observed in the occurrence of AEFIs across the three doses. Conclusions: The pentavalent vaccine was found to be safe for infants in the Federal Capital Territory (FCT), Nigeria, with the observed AEFIs being generally mild and decreasing in frequency with subsequent doses. Recommendations: Further studies should be conducted to monitor long-term safety and potential rare adverse effects of pentavalent vaccines. Additionally, public health education should emphasize the safety and benefits of pentavalent vaccines to increase vaccination rates and reduce vaccine hesitancy. Significance Statement: This study underscores the safety of pentavalent vaccines in infants, reinforcing their role in preventing multiple serious diseases through a single immunization schedule. The findings support the continued use and promotion of pentavalent vaccines in public health programs, particularly in regions with high infant mortality rates and limited healthcare resources.