A case-control analysis was performed to evaluate the association of 15 potential risk factors with postoperative infection in neurosurgical patients. All infections that developed postoperatively on the neurosurgical service at the University of Minnesota from January, 1970, to March, 1984, were identified. Among the 9202 operations performed during that time, 101 infections occurred for a rate of 1.1%. Three risk factors showed significant association with postoperative infection: cerebrospinal fluid (CSF) leak, concurrent noncentral nervous system (CNS) infection, and perioperative antibiotic therapy. The presence of a CSF leak and a concurrent non-CNS infection increased the estimated relative risk of infection to 13:1 and 6:1, respectively. The use of perioperative antibiotics was associated with a decrease in the risk of infection to approximately 20% of the control level. Three other risk factors (paranasal sinus entry, placement of a foreign body, and use of a postoperative drain) appeared to be associated with increased risk of infection, although statistical significance was not demonstrated. None of the remaining nine risk factors studied showed any suggestion of increased risk of infection.