Impacted and semi-impacted third molar surgery is a frequent dental procedure. Due to potentially major tissue manipulation during surgery, antibiotic prophylaxis may be indicated to prevent infection of the surgical wound. This study evaluated the surgical conditions of patients following extraction of impacted and semi-impacted third molars with or without prior antibiotic prophylaxis. Signs of infection and inflammation, postoperative pain level and efficacy of the prescribed drugs were recorded. This was a prospective, randomized, double blind clinical trial with split-mouth design. A total of 23 healthy (ASA I) volunteers with indication for bilateral mandibular third molar extraction were recruited, totaling 46 surgical procedures. One hour prior to the procedure, volunteers received 1g of amoxicillin or placebo and a drug for pain prevention and control. The surgical acts were performed by last-year dental students. Postoperative pain was assessed using a visual analogue scale and an 11-point box scale at selected postoperative intervals of 4 h, 12 h, and 24 h. After seven postoperative days, study volunteers were examined for clinical signs of infection and/or inflammation, such as pus, intra and extraoral swelling, trismus, heat, flushing and temperature change. There were only two cases of postoperative complications, one of intraoral edema (placebo group) and one of trismus (antibiotic prophylaxis group). There were no statistically significant differences for any of the indicative signs of infection. The pain scales revealed no differences between pain levels in both groups at all times evaluated, regardless of the pain scale used (P > 0.05). To conclude, the low infection rate observed in our study does not reflect any need for antibiotic prescription in systemically healthy patients. The adverse effects of antibiotics in addition to selection for resistant bacteria outweigh the benefits of antibiotic prophylaxis in healthy (ASA I) patients.