BACKGROUND: There is limited evidence on the use of antibiotic prophylaxis prior to endoscopic ultrasound-guided fine-needle aspiration of pancreatic cysts. The aim of this meta-analysis was to evaluate the efficacy of antibiotic prophylaxis in this setting.RESEARCH DESIGN AND METHODS: Bibliographic search was performed through January 2020. The primary outcome was infection rate. Additional endpoints were severe infection rate and overall rates of adverse events.RESULTS: Six studies, of which one was a randomized controlled trial and five were retrospective, with 1706 patients were included. Most patients were female, and body/tail was the most frequent location of cystic lesions. Overall, eight infectious events were observed in the antibiotic group (0.77%), whereas 12 events were registered in the control group (1.7%), with no difference in terms of infection rate (odds ratio 0.65, 95% confidence interval 0.24-1.78; p = 0.40). Again, no difference was observed between the two study groups in terms of either severe infection (odds ratio 0.88, 0.13-5.82; p = 0.89) and overall adverse event rate (odds ratio 1.09, 0.73-1.65; p = 0.67).CONCLUSIONS: Prophylactic antibiotics do not seem to substantially reduce the risk of infections after endoscopic ultrasound-guided fine-needle aspiration of pancreatic cystic lesions, and routine use of prophylactic antibiotics should be questioned.