Background: The benefit of prophylactic antibiotic use in endoscopic endonasal transsphenoidal surgery (EETS) for pituitary lesions is controversial. Many surgeons administer antibiotics perioperatively not based on clear guidelines but “to be safe”. Methods: A systematic review using PRISMA guidelines was performed to assess the efficacy of perioperative antibiotic use to prevent infectious complications in patients undergoing EETS. Inclusion criteria: randomized controlled trials, systematic reviews, observational studies, and case series. Data extracted: study design, year of publication, sample size, surgery type, perioperative antibacterial treatment (antibiotic, dose, and duration), number of patients with 30-days post-operative meningitis and/or sinusitis. End points: rates of meningitis and sinusitis post-EETS. Results: A total of 280 articles were identified. Four observational studies met inclusion criteria. Based on GRADE score these studies were considered low in quality. 633 patients were -included in those studies. The most common antibiotics used were cefazolin and ceftazidime. The rate of infection ranged from 0.5% to 3.1 % for meningitis as the most common infection. Conclusions: The need to use antibiotic(s) perioperatively is not clear in patients with pituitary lesions undergoing EETS. Randomized control trials are needed to evaluate the efficacy of prophylactic antibiotic use in patients with pituitary lesions undergoing EETS.