INTRODUCTION: Several recent studies have reported accurate and reliable use of patient-specific cutting guides (PSCG) for medial opening-wedge high tibial osteotomy (OW-HTO); however, a majority of these are small cases series or ex-vivo reports. The hypothesis of this study was that performing an OW-HTO with PSCG results in a reliable and accurate correction with good or satisfactory patient-reported functional outcomes at a mean of two years. We also hypothesized that the use of PSCG would not increase the rate of specific or non-specific complications. METHODS: In this single-centre, observational study, a prospective cohort of a hundred patients (age \textless 60 years with isolated medial knee osteoarthritis and significant metaphyseal tibial vara) were included between February 2014 and November 2017 to investigate the safety and accuracy of OW-HTO using PSCG. The accuracy of post-operative alignment was defined by the difference between the desired correction defined pre-operatively and the correction obtained post-operatively measured on CT scan (ΔHKA, ΔMPTA, ΔPPTA). Functional outcomes were evaluated by the difference between the value obtained in the pre-operative questionnaire and that obtained at the last follow-up (mean 2 years) using the KOOS and UCLA activity scale. Intra-operative and post-operative complications were recorded. RESULTS: The mean patient age was 44.17 ± 6.77 years; no patient was lost to follow-up at a mean of two years. The mean ΔHKA was 1 ± 0.95°, the mean ΔMPTA was 0.54 ± 0.63°, and the mean ΔPPTA was 0.43 ± 0.8°. No significant differences (all p values \textgreater 0.05) were observed between the desired correction defined pre-operatively and the correction obtained post-operatively (ΔHKA, ΔMPTA, ΔPPTA). An improvement of 27 ± 25 for the KOOS Pain, 28 ± 26 for the KOOS symptoms, 27 ± 28 for the KOOS ADL, 26 ± 33 for the KOOS sport/rec, 28 ± 38 for the KOOS QOL, and 2.6 ± 2.4 for the UCLA was obtained as compared with the pre-operative values (all p \textless 0.0001). No procedures observed were abandoned, and the PSCG was well positioned in all cases. The overall complication rate was 32% up to two years post-operatively, most of them being classed as minor events (28%). CONCLUSION: Performing an OW-HTO with PSCG produces an accurate correction with good functional outcomes at a mean of two years. Furthermore, there is no increase in the rate of specific or non-specific complications. A study to assess the reproducibility of this technique, regardless of the surgical level, is needed.