Background: Postoperative meningitis and surgical site infections (SSI) is a challenging issue that may result in serious morbidity and mortality. This study aims at decreasing the incidence and identifying the causative pathogens of postoperative meningitis and SSI in patients undergoing craniotomies. Results: The study is a cohort study designed in ASA I and II patients undergoing elective craniotomies for brain tumors, to compare the incidence of meningitis and surgical sites infections between an intervention group who received proposed prophylactic antibiotics from April 2014 to April 2015 and a control group from April 2013 to April 2014 when prophylactic antibiotic protocols were lacking. 488 (four hundred and eighty eight) patients were included. The incidence of meningitis was 3.5% in the pre-protocol group and 2.1% in the post-protocol group (p = 0.331), while that of surgical site infections was 4% in the pre-protocol group and 3.5% in the post-protocol group (p = 0.747). The following pathogens [Pseudomonas,Enterococci, Ecoli and MRSA] decreased, while [klebsiella, Stahpaureus and Acinetobacter] increased after application of the protocol. Conclusions: Although the incidence of both meningitis and surgical site infections decreased after application of the prophylactic antibiotic protocol this was not statistically significant. The main pathogens were mostly gram-negative bacteria which could indicate an alteration of the causative organisms and may modify the choice of prophylactic antibiotics.