The aim of this study was to document, at mid-term follow-up, the clinical and MRI outcome of a polyurethane-based cell-free scaffold implanted to treat painful partial meniscus loss.Eighteen consecutive patients were enrolled and treated with arthroscopic polyurethane meniscal scaffold implantation and, in case of other comorbidities, with concurrent surgical procedures: 16 patients (9 men and 7 women, mean age 45 ± 13 years, mean BMI 25 ± 3, 12 medial and 4 lateral implants) were prospectively evaluated with the subjective and objective IKDC and the Tegner scores at 24, 36, 48, 60, and 72 months of follow-up. Eleven patients were also evaluated by 1.5-T MRI at the final follow-up.The IKDC subjective score showed a significant improvement from baseline to 24 months (45.6 ± 17.5 and 75.3 ± 14.8, respectively; p = 0.02) and subsequent stable results over time for up to 72 months (final score 75.0 ± 16.8). The Tegner score improvement between pre-operative status and final follow-up was also significant (p = 0.039). Nevertheless, the final score remained significantly lower than the pre-injury sports activity level (p = 0.027). High-resolution MRIs documented the presence of abnormal findings in terms of morphology, signal intensity, and interface between the implant and the native meniscus. Implant extrusion and bone oedema at the treated compartment were also observed in most of the cases, even though no correlation was found between imaging findings and clinical outcome.The present study reports satisfactory clinical outcomes at mid-term follow-up after polyurethane-based meniscal cell-free scaffold implantation. The treatment was effective both in cases of isolated partial meniscal lesions and in complex cases requiring the combination with other surgical procedures. On the other hand, a high rate of altered MRI aspects was documented. However, no correlation was found between the altered imaging parameters and the overall positive clinical findings, thus supporting the use of this procedure to treat painful partial meniscus loss.Case series, Level IV.