Background: Hepatitis B birth dose vaccination is an essential preventive strategy against neonatal infection and is generally safe, with only minor adverse effects. However, rare complications such as injection site pyogenic abscess may occur, often related to breaches in aseptic technique during vaccine administration. Case Report: We report a four-week-old female infant who developed a progressively enlarging, tender swelling over the anterolateral aspect of the left thigh following Hepatitis B birth dose vaccination. Clinical evaluation and investigations suggested a post-vaccination abscess. Due to poor response to initial medical management, incision and drainage were performed, yielding purulent material. Culture grew methicillin-resistant Staphylococcus aureus (MRSA). The infant was treated with appropriate antibiotics for three weeks and recovered completely. Conclusion: Pyogenic abscess following Hepatitis B vaccination is a rare but preventable adverse event. Strict adherence to aseptic techniques, appropriate injection practices, and proper training of healthcare workers are crucial to minimize such complications.