Purpose Patient-specific cutting guides (PSCGs) have been advocated to improve the accuracy of deformity correction in opening-wedge high-tibial osteotomies (HTO). It was hypothesized that PSCGs for HTO would have a short learning curve. Therefore, the goals of this study were to determine the surgeons learning curve for PSCGs used for openingwedge HTO assessing: the operating time, surgeons comfort levels, number of fluoroscopic images, accuracy of postoperative limb alignment and functional outcomes. Methods This prospective cohort study included 71 consecutive opening-wedge HTO with PSCGs performed by three different surgeons with different experiences. The operating time, the surgeon's anxiety levels evaluated using the Spielberger State-Trait Anxiety Inventory (STAI), the number of fluoroscopic images was systematically and prospectively collected. The accuracy of the postoperative alignment was defined by the difference between the preoperative targeted correction and the final post-operative correction both measured on standardized CT-scans using the same protocol (ΔHKA, ΔMPTA, ΔPPTA). Functional outcomes were evaluated at 1 year using the different subscores of the KOOS. Cumulative summation (CUSUM) analyses were used to assess learning curves. Results The use of PSCGs in HTO surgery was associated with a learning curve of 10 cases to optimize operative time (mean operative time 26.3 min ± 8.8), 8 cases to lessen surgeon anxiety levels, and 9 cases to decrease the number of fluoroscopic images to an average of 4.3 ± 1.2. Cumulative PSCGs experience did not affect accuracy of post-operative limb alignment with a mean: ΔHKA = 1.0° ± 1.0°, ΔMPTA = 0.5° ± 0.6° and ΔPPTA = 0.4° ± 0.8°. No significant difference was observed between the three surgeons for these three parameters. There was no statistical correlation between the number of procedures performed and the patient's functional outcomes. Conclusion The use of PSCGs requires a short learning curve to optimize operating time, reduce the use of fluoroscopy and lessen surgeon's anxiety levels. Additionally, this learning phase does not affect the accuracy of the postoperative correction and the functional results at 1 year. Level of evidence II: prospective observational study.