introductionSurgical site infections pose a significant problem in the treatment of neurosurgical procedures, regardless of the application of perioperative prophylaxis with systemic antibiotics. The infection rate in these procedures ranges from less than 1% to above 15%. Different antibiotics and administration regimes have been used in the perioperative prophylaxis so far, and there are numerous comparative studies regarding their efficiency, however, it is generally indicated that the choice thereof should be based on information and local specifics connected to the most probable bacterial causers, which would possibly contaminate the surgical site and cause infection, and moreover, the mandatory compliance with the principles of providing adequate concentration of the drug at the time of the anticipated contamination.objective Comparing the protective effect of two perioperative prophylactic antibiotic regimes using cefuroxime (second generation cephalosporin) and ceftriaxone (third generation cephalosporin) in the prevention of postoperative surgical site infections after elective and urgent cranial and spinal neurosurgical procedures at the University Clinic for Neurosurgery in Skopje in the period of the first three months of 2016.design of the study Prospective randomized comparative study. outcome measuresEstablishing the clinical outcome represented as prevalence of superficial and deep incision and organ/space postoperative surgical site infections. Material and methodWe analyzed prospectively 40 patients who received parenteral antibiotic prophylaxis with two antibiotic regimes one hour before the routine neurosurgical cranial and spinal surgical procedures; the patients were randomized in two groups, according to the order of admission and participation in the study, alternately, non-selectively, those persons who fulfilled inclusion criteria were placed in one of the two programmed regimes with cefuroxime in the first, and cefotaxime in the second compared group. All relevant demographic and perioperative patient data were analyzed for both comparative groups, especially the factors known to cause disposition (predisposition) to infections. The prevalence of postoperative infections was evaluated as the primary outcome corresponding author: Ass. D-r Aleksandra Dimovska Gavrilovska Dr. Med