Objective The aim of this study was to assess the results of open reduction and internal fixation (OR/IF) of isolated mandibular fracture under regional anesthesia using mandibular nerve block. Patients and methods This prospective study was carried out on 44 patients who had isolated traumatic parasymphyseal mandibular fractures. All patients were managed by OR/IF by two titanium miniplates using manual maxillomandibular fixation (MMF). All patients were sedated by (0.05 mg/kg) midazolam and (2 μg/kg) fentanyl. The patients were randomly classified into two groups: the control group (22 patients) treated under general anesthesia (GA) and the study group (22 patients) repaired under regional anesthesia. The results were assessed as regards dental occlusion, average intrinsic vertical mouth opening, actual operative time, complication, tolerance and patient’s satisfaction, and postoperative hospital stay time. Results Both groups were matched for age and sex. There were no statistically significant differences of the postoperative complication, dental occlusion, and mouth opening between both groups. Duration for anesthesia induction, intubation, and anesthesia recovery was not needed in regional anesthesia. Regional anesthesia was tolerable and highly satisfactory in all patients with no intraoperative or postoperative anesthesia-related problems and no reported complications Conclusion Regional anesthesia can effectively replace GA inselected cases of mandibular fracture obviating the risks of GA.