BACKGROUND: The evidence guiding management of cranial surgical site infections (SSIs) is sparse with limited data on optimal duration of antimicrobial therapy. There is a lack of published data on the approach to and outcomes of cranial SSI management. METHODS: We retrospectively reviewed patients from Oxford University Hospitals, United Kingdom, requiring revision surgery for SSI following primary craniotomy, craniectomy, and cranioplasty between January 2019 and April 2022 and reviewed outcomes at 24 months. Data were collected on patient characteristics, diagnosis, management, and outcome. Analysis was performed in R. RESULTS: Of 94 patients included, 44% were male and the median age was 51 years (IQR, 42-63). During surgical inspection, 40% of infections involved only superficial structures, 33% the extradural space, and 27% extended to the subdural space. Staphylococcus aureus (24%) and Cutibacterium acnes (22%) were the most frequently identified organisms, while all gram-negative bacilli combined accounted for 26% of cases. Rates of repeat surgery for infection were not significantly different between superficial and deep SSI (26% vs 28%, P = .499). On univariate analysis, corticosteroid use (odds ratio, 3.51; 95% CI, 1.24-10.00; P = .018) and prolonged antibiotic therapy (odds ratio, 1.34; 95% CI, 1.11-1.62; P = .002) were significantly associated with adverse outcome. CONCLUSIONS: These findings underscore the complexity of cranial SSIs and variation in presentation. Failure in this cohort was not uncommon, and practitioners should be particularly vigilant in the management of "superficial" infections. Developing a national consensus guideline would be an important step toward standardizing care and improving patient outcomes in this challenging cohort.