OBJECTIVE The purpose of the present study was to identify the risk factors for major complications developing during the operative treatment of mandibular fractures. METHODS We conducted a retrospective medical record review of patients who had undergone open reduction, internal fixation of mandibular fractures from August 1, 2012 to December 31, 2014 at a large, urban teaching hospital and level 1 trauma center. The outcome variable of interest was major complications, defined as the occurrence of any one of the following events: hospital readmission, return to the operating room, and a prolonged, unexpected postoperative stay. Multiple demographic, social, medical, injury-related, and treatment-related variables were recorded during the medical record review. The relationships between these variables and our outcome variable were analyzed using univariate and multivariable logistic regression analyses. RESULTS A total of 317 patients met the inclusion criteria. The hospital readmission rate was 7.2%, the reoperation rate was 9.5%, and the rate of unplanned, prolonged admission was 0.6%, for a total major complication rate of 11.4%. Eight variables reached statistical significance in their association with the occurrence of major complications. These were the presence of medical comorbidities, a diagnosis of depression, a diagnosis of a psychiatric disorder, incarceration, interpersonal violence as a mechanism of injury, the presence of a left angle fracture, the removal of a tooth in the line of fracture, and patient noncompliance. On multivariable analysis, patient noncompliance, depression, the presence of a left angle fracture, and the removal of a tooth in the line of fracture continued to have statistically significant associations with the occurrence of major complications. CONCLUSIONS The identification of risk factors for the development of complications in mandibular trauma is a primary concern for surgeons in the modern healthcare system. The present study identified a number of variables significantly associated with an increased risk of the occurrence of major complications, and special consideration should be given to patients with these risk factors.