Purpose: The objectives of this study were to determine the prevalence, incidence, and risk factors for postoperative surgical site infections (SSIs) after craniotomy. Methods: This study was a retrospective case-control study of 103 patients who had craniotomies between March 2007 and December 2008. A retrospective review of prospectively collected databases of consecutive patients who underwent craniotomy was done. SSIs were defined by using the Centers for Disease Control criteria. Twenty-six cases (infection) and 77 controls (no infection) were matched for age, gender and time of surgery. Descriptive analysis, t-test, $chi^2$-test and logistic regression analyses were used for data analysis. Results: The statistical difference between cases and controls was significant for hospital length of stay (>14 days), intensive care unit stay more than 15 days, Glasgrow Coma Scale (GCS) score (${leq}7$ days), extra-ventricular drainage and coexistent infection. Risk factors were identified by logistic regression and included hospital length of stay of more than 14 days (odds ratio [OR]=23.39, 95% confidence interval [CI]=2.53-216.11) and GCS score (${leq}7$ scores) (OR=4.71, 95% CI=1.64-13.50). Conclusion: The results of this study show that patients are at high risk for infection when they have a low level of consciousness or their length hospital stay is long term. Nurses have to take an active and continuous approach to infection control to help with patients having these risk factors.