Background: Unicondylar knee arthroplasty was introduced in the late 1960s and remains a topic of controversial discussion. Patient-specific instruments and patient-specific implants are not yet the standard of care. The question remains whether this time-consuming and costly technique can be beneficial for the patient. The aim of this study was to evaluate whether a custom-made unicondylar knee arthroplasty leads to improved patient-reported outcome. Methods: This retrospective study evaluates the patient-reported outcome after custom-made unicondylar knee arthroplasty (CM-UKA, ConforMIS (TM) iUni (R) G2, ConforMIS Inc., Billerica, MA, USA). We evaluated 29 patients (31 knees) at an average of 2.4 years (range 1.2-3.6 years) after operation for unicondylar osteoarthritis of the knee. The target zone for the postoperative leg axis was a slight under-correction of 0-2 degrees varus. Follow-up evaluation included the Forgotten Joint Score (FJS), the Knee Society Score (KSS), a Visual Analogue Scale (VAS) and a radiographic evaluation including a long-leg radiograph. Primary outcome measure was patient satisfaction based on the Forgotten Joint Score. Results: We found an excellent postoperative health-related quality of life with a mean FJS of 76.8 (SD 17.9) indicating a low level of joint awareness after CM-UKA. The mean preoperative KSS was 66.0 (SD 13.71) and 59.4 (17.9) for the KSS function score. The increase was 22.8 points for the KSS knee score (p < 0.0001) and 34.8 points for the KSS function score (p < 0.0001). The VAS for pain decreased from a mean of 5.4 (SD 1.8) to 1.1 (SD 1.2) (p < 0.0001). The malalignment rate with a postoperative deviation of more than 2 degrees in the leg axis was 29%. There was no evidence of component loosening after a mean follow-up of 2.4 years. Conclusions: Custom-made unicondylar knee arthroplasty (CM-UKA) can provide improved clinical and functional outcomes for patients with isolated knee osteoarthritis of the medial compartment. We found excellent results regarding patient satisfaction and a low malalignment rate for CM-UKA. Further studies are needed to investigate long-term survivorship of the implant.