Background: The effect of prophylactic antibiotics on post-operative infection rates in isolated mandibular fractures has been debated for many years. Some surgeons advocate prophylactic antibiotic therapy in specific circumstances such as open fractures or delayed repair, while others question its actual benefit in any mandibular fracture. Purpose: To determine the impact of prophylactic antibiotics on post-operative infection rates in patients with isolated mandibular fractures. Patients and Methods: A retrospective chart review was performed on all patients presenting with isolated mandibular fractures from the time period of 12/1/93 to 12/1/01. Patients were separated into study groups based on whether the fracture was repaired within 72 hours (non-delayed) or after 72 hours (delayed) of initial injury. In addition, patients were divided into groups based on whether the fracture was open (laceration in oral mucosa) or closed (no laceration in the oral mucosa). Prophylactic pre-operative antibiotics most commonly consisted of clindamycin and levofloxacin. Otolaryngologists, plastic surgeons and oral maxillofacial surgeons performed the reparative surgery. All patients received peri-operative IV antibiotics and post-operative oral antibiotics and oral rinses. Results: A total of 417 patients were included in the study. The average time to repair of fracture was 34 hours in the non-delayed group and 106 hours in the delayed group. Delayed treatment was most commonly due to delay in presentation to the hospital. There were no significant differences in patient demographics, mechanisms of injury, fracture location or methods of fixation between the two groups. An open-delayed repair of a mandible fracture was found to have a significantly higher rate of post-operative infection (10.2%) when compared to all other categories (all less than 2.5%). Conclusion: Delaying the repair of isolated mandibular fractures greater than 72 hours or having a fracture site exposed through a tear in the oral mucosa do not by themselves significantly increase the rate of post-operative infection. However, if the repair of an open fracture is anticipated to be delayed longer than 72 hours, prophylactic pre-operative antibiotics should be considered therapeutic given the significant increase in risk of post-operative infections in this group of patients.