The objective of this study was to determine the effect of antibiotic prophylaxis in preventing postoperative infections after extraction of impacted mandibular third molars. A Parallel-group, randomized, blind, placebo-controlled trial was performed. 154 patients were randomly allocated to 2 groups; experimental (n=77) receiving 2g amoxicillin 1 hour prior to surgery and control (n=77) receiving placebo. Primary outcome was postoperative infections and secondary outcome was the need for rescue analgesia. 4.5% of patients developed postoperative infections, five patients of the control group (4 alveolar osteitis, 1 surgical site infection) and two of the experimental group (1 alveolar osteitis, 1 surgical site infection). Difference between groups was not statistically significant, RR=0.4 (95%CI 0.08-1.99, ?=0.41) NNTB=26. Rescue analgesia intake was significantly higher in the control group (41 vs 18 patients of experimental group) RR=0.49 (95%CI 0.32-0.75, ?<0.05) NNTB=3. The use of 2g amoxicillin 1 hour before surgery was not effective in significantly reducing the risk of postoperative infections from impacted mandibular third molars extraction, when compared to placebo. Nevertheless, antibiotic prophylaxis was associated with a reduced need for rescue analgesia.