The aims of this study were to compare the presurgical conditions, surgical changes, and postsurgical changes in patients with skeletal Class III malocclusion with different degrees of horizontal relapse after mandibular setback surgery (MS) with minimal presurgical orthodontics (MPO) and to identify the factors contributing to this relapse. For this retrospective study, 33 consecutive patients who underwent MS-MPO were selected. Lateral cephalograms were taken preoperatively (T0), 1month after surgery (T1), and at orthodontic debonding (T2). Patients were divided into low relapse (LR; n=18; relapse, <1mm) and high relapse (HR; n=15; relapse, >2mm) groups based on the cephalometric distance of mandibular horizontal relapse. Paired t test, independent t test, and Pearson correlation analysis were used to evaluate surgical (T0 to T1) and postsurgical (T1 to T2) changes in the skeletodental variables and to explore the relation between surgical changes and horizontal relapse. Compared with the LR group, the HR group exhibited more upward movement with counterclockwise rotation of the mandible from T1 to T2. The HR group presented at T0 with a more prognathic mandible, greater vertical facial height, and a positive overbite. In addition, the HR group presented more posterior movement with clockwise rotation of the mandible, increased overjet, and decreased overbite from T0 to T1. Horizontal relapse of the mandible was positively correlated with the amount of setback and clockwise rotation of the mandible and the change in overjet and was negatively correlated with the change in overbite. Mandibular instability was related to the extent of setback and clockwise rotation of the mandible, decreased overbite, and increased overjet during MS-MPO.