Background. A consensus conference recommended empirical antibiotic therapy for all patients with postoperative meningitis and treatment withdrawal after 48 or 72 h if cerebrospinal fluid culture results are negative. However, this approach is not universally accepted and has not been assessed in clinical trials. Methods. We performed a cohort study of all patients who received a diagnosis of postoperative meningitis from January 1998 through May 2005 in a teaching hospital. From January 1998 through September 2003 (control period), guidelines were lacking or were not implemented. From October 2003 through May 2005 (interventional period), all patients received a predefined intravenous antibiotic therapy that was discontinued on the third day if the meningitis was considered aseptic. Clinical outcome and duration of antibiotic therapy were analyzed for each patient. Results. Seventy-five episodes of postoperative meningitis (21 cases of bacterial meningitis and 54 cases of aseptic meningitis) were investigated. Patients with aseptic meningitis received antibiotic treatment for a mean +/- standard deviation duration 11 +/- 5 days during the control period and 3.5 +/- 2 days during the intervention period (P = .001). The duration of antibiotic treatment for bacterial meningitis was not significantly different between the 2 periods. All episodes of bacterial and aseptic meningitis were cured, and complications were rare during both periods. Conclusions. Stopping antibiotic treatment after 3 days is effective and safe for patients with postoperative meningitis whose cerebrospinal fluid culture results are negative.