Purpose: The purpose of this study was to determine the necessity and/or effectiveness of postoperative antibiotics in the treatment of mandible fractures. Materials and Methods: This study is a prospective, randomized trial composed of patients who presented for operative treatment of open mandibular fractures and subsequently underwent open reduction and internal fixation at 1 institution. Mandibular fractures treated by an intraoral and/or extraoral open reduction with internal fixation were included in this study. The patients were randomly divided into 2 groups based on whether or not they received postoperative antibiotics. Both groups received preoperative antibiotics of various regimens as well as intraoperative antibiotics on the day of surgery. Group Ab patients received 2.4 mIU of intramuscular penicillin G benzathine, or if allergic, a 5- to 7-day regimen of oral clindamycin. Group non-Ab patients received no antibiotics postoperatively. Patients followed between 5 and 8 weeks were included in the data set. Results: A total of 291 patients were enrolled in the study, of which 181 patients met the inclusion criteria. Group Ab included 81 and group non-Ab 100 patients. Twenty-two patients had evidence of infection noted within the 8-week follow-up period. There were 8 infections in group Ab and 14 infections in group non-Ab. Statistical analysis with the Pearson Chi-square and Student's t test showed no statistically significant difference (P = .399) between groups Ab and non-Ab. Conclusion: This study could not prove any statistically significant benefit to the administration of postoperative antibiotics in patients undergoing open reduction and internal fixation of mandibular fractures.