ABSTRACT: We previously conducted a single-arm, prospective study in which 31 patients (mean age [and standard deviation], 42.5 ± 11.3 years) with cartilage lesions were treated with use of the BioPoly Partial Resurfacing Knee Implant. Treatment outcomes were compared with those reported for the standard of care, microfracture. We found that the mean KOOS (Knee injury and Osteoarthritis Outcome Score) Quality of Life score at 5 years in the BioPoly cohort was noninferior to (p = 0.004), and indeed greater than (p = 0.021), that in the microfracture cohort. The BioPoly cohort demonstrated improvement in the mean scores for all KOOS domains at every postoperative time point (p < 0.025). The mean score for the visual analog scale (VAS) for pain significantly improved (p < 0.025) at all time points up to 4 years and trended toward significant improvement at 5 years (p = 0.027). This study indicated that the BioPoly implant was safe, provided significant improvement starting at 6 months and continuing to 5 years, and provided greater improvement than microfracture for some outcome measures. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.