© 2014 Elsevier Inc. Objective: Bone flap infections after autogenous cranioplasty can present a diagnostic and management challenge. Little is known about the clinical, radiological, and microbiological profile of these patients. Methods: Patients who developed bone flap infective complications requiring explantation after autogenous cranioplasties between 1999 and 2009 were identified. Their prospectively collected demographic details, clinical presentation, radiological features, surgical intervention, microbiological profile, and treatment outcomes were retrospectively reviewed. Results: During the study period, 179 cranioplasties were performed with frozen autogenous skull flaps. Seventeen patients (10%, median age 25 years) experienced deep infections that necessitated flap removal and antimicrobial treatment. Although fever, swelling of the scalp, and local inflammation were present in majority of patients (76.5%), inflammatory markers were abnormal only in 33%. Computed tomography imaging features included extra-axial collection (76.5%), subgaleal collection or galeal swelling (70.6%), cerebritis (37.5%), and osteomyelitis (23.5%). Positive bacterial cultures were obtained from all (100%) explanted bone flaps, including gram-positive (82.3 %) and -negative (17.7%) organisms. A significant proportion (29.4%) of patients presented with complications late during follow-up (>6 weeks); 60% of these were attributable to Propionibacterium acnes infection. Conclusions: Clinical assessment is critical to the diagnosis of bone-flap infection. A high index of suspicion is necessary because late presentations are possible. Empirical antimicrobial treatment should include gram-negative coverage.