Purpose Patient-specific instruments (PSI) have been designed to improve the accuracy of performing opening-wedge high-tibial osteotomies (OW-HTO). This study aims to evaluate the lower limb alignment, by comparing pre-operative desired correction to post-operative achieved correction, the difference in surgical time and number of radiological exposures in OW-HTO using patient-specific instruments (PSI) versus conventional osteotomies and the specific and non-specific complications that occurred. Methods We performed a single-centre, retrospective, observational study, including 25 consecutive patients undergoing OW-HTO using PSI, from January 2019 to October 2020. Results Pre-operatively, the mean hip-knee angle (HKA) was 167°, the mean tibial slope was 7.9° and the mean medial proximal tibial angle (MPTA) was 82.5°. Post-operatively, the mean HKA was 182.2° (180.1–184.7°), the tibial slope was 6.5° (4.2–12.9°) and the MPTA was 92.8° (90.6–93°). In both coronal and sagittal plane, all knees were within 2° from the planned value. The mean tourniquet time, by which the surgical time was measured, was 40 minutes and the average number of intra-operative fluoroscopic images was 10 (range: 7–14), significantly less than when using conventional techniques. Conclusions The use of PSI in OW-HTO allows accurate achievement of the desired correction, while shortening the OR time. The number of radiological exposures is also decreased, in comparison with the conventional osteotomies.