Introduction: Antibiotic prophylaxis is controversial, and its inappropriate use exposes patients to the risk of adverse reactions and the development of bacterial resistance. Objective: Carry out a systematic review of randomized clinical trials evaluating the efficacy of antibiotic prophylaxis for the reduction of postoperative infections after extraction of impacted third molars. Methods: The search for clinical trials was conducted in the databases ScienceDirect, Clinicaltrials.gov and Scopus. The primary variables considered were presence of postoperative infections (of the wound and/or alveolitis), adverse reactions, trismus and pain. A meta-analysis was made of homogeneous studies applying the random effects model. The risk of bias in the trials included was evaluated using the Cochrane guide. The inverse variance approach and the random effects method were used for estimation of the global relative risk. Results: Fourteen clinical trials were analyzed qualitatively and 9 quantitatively. Of the total 874 patients, 49 (5.6%) developed postoperative infections (16 / 446 for the experimental group and 33 / 428 for the placebo group). The meta-analysis found a global relative risk of 0,5 (CI 95 %: 0,27-0,94). Bias risk for studies using only amoxicillin as a prophylactic measure was 0,53 (CI 95 %: 0,27-1,03). The main adverse reactions were diarrhea, gastrointestinal reactions, fever and abdominal pain. Conclusions: The systemic antibiotics administered before the surgery were effective to reduce the frequency of appearance of postoperative infections after extraction of impacted third molars.