The posterior tibial slope of the tibiofemoral joint changes after medial open wedge high tibial osteotomy (MOWHTO), but little is known about the effect of the sagittal osteotomy inclination angle on the change in the posterior tibial slope of the tibiofemoral joint. The purpose of this study was to investigate the effect of the osteotomy inclination angle in the sagittal plane on changes in the posterior tibial slope after MOWHTO by comparing how anterior and posterior inclination affect the posterior tibial slope of the tibiofemoral joint. The correlation between the osteotomy inclination angle and the postoperative posterior tibial slope angle was also assessed. Between May 2011 and November 2017, 80 patients with medial compartment osteoarthritis who underwent MOWHTO were included. The patients were divided into two groups according to the sagittal osteotomy inclination angle on the 3D reconstructed model. Patients with an osteotomy line inclined anteriorly to the medial tibial plateau line were classified into group A (58 patients). Patients with posteriorly inclined osteotomy line were classified as group P (22 patients). In the 3D reconstructed model, the preoperative and postoperative posterior tibial slope, osteotomy inclination angle relative to medial tibial plateau line in sagittal plane, and gap distance and ratio of the anterior and posterior osteotomy openings were measured. The preoperative and postoperative hip-knee-ankle angle, weight-bearing line ratio, and posterior tibial slope were also measured using plain radiographs. In the 3D reconstructed model, the postoperative posterior tibial slope significantly increased in group A (preoperative value = 9.7 ± 2.9°, postoperative value = 10.7 ± 3.0°, p < 0.001) and decreased in group P (preoperative value = 8.7 ± 2.7°, postoperative value = 7.7 ± 2.7°, p < 0.001). The postoperative posterior tibial slope (group A = 10.7 ± 3.0°, group P = 7.7 ± 2.7°, p < 0.001) and posterior tibial slope change before and after surgery (group A = 1.0 ± 0.8°, group P = −0.9 ± 0.8°, p < 0.001) also differed significantly between the groups. The Pearson correlation coefficient was 0.875 (p < 0.001) for the osteotomy inclination angle, and multivariate regression analysis showed that the only significant factor among the variables was the sagittal osteotomy inclination angle (β coefficient = 0.216, p < 0.001). The posterior tibial slope changed according to the osteotomy inclination angle in the sagittal plane after MOWHTO. The postoperative posterior tibial slope tended to increase when the osteotomy line was inclined anteriorly with respect to the medial tibial plateau line but decreased when the osteotomy line was inclined posteriorly. To avoid inadvertent change of posterior tibial slope, close attention needs to be paid to maintaining the sagittal osteotomy line parallel to the medial joint line during MOWHTO.