Objectives We tended to evaluate the effectiveness of prophylactic antibiotics for preventing meningitis in patients with BSF. Method We searched the Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to September 2005), EMBASE (1974 to June 2005), and LILACS (1982 to September 2005). We also performed an electronic search of meeting proceedings from the American Association of Neurological Surgeons (1997 to September 2005) and handsearched the abstracts of meeting proceedings of the European Association of Neurosurgical Societies (1995, 1999 and 2003). Randomized controlled trials (RCTs) comparing any antibiotic versus placebo or no intervention were identified. We also identified non-RCTs to perform a separate meta-analysis to compare results. At least two authors independently appraised the quality and extracted the data of each trial. Meta-analysis was conducted using RevMan 4.2 software. Results Five RCTs and 17 non-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention in patients with BSF were identified. Most trials presented insufficient methodological detail. All studies included meningitis in their primary outcome. Overall, we evaluated 208 participants from the four RCTs that were considered suitable for inclusion in the meta-analysis. There were no significant differences between antibiotic prophylaxis groups and control groups in terms of reduction of the frequency of meningitis, all-cause mortality, meningitis-related mortality, and need for surgical correction in patients with CSF leakage. We performed a subgroup analysis to evaluate the primary outcome in patients with and without CSF leakage. We also completed a meta-analysis of all the identified controlled non-RCTs (enrolling a total of 2 168 patients), producing results consistent with the randomised data. Conclusions Currently available evidence from RCTs does not support prophylactic antibiotic use in patients with BSF, whether there is evidence of CSF leakage or not. Until more research is completed, the effectiveness of antibiotics in patients with BSF cannot be determined because studies published to date are flawed by biases. Large, appropriately designed RCTs are needed.