© 2020, Istituto Ortopedico Rizzoli.Purpose: This study aimed to assess the impact of biodegradable polyurethane meniscus scaffold implantation (BPMSI) on muscle strength and balance in comparison with the healthy contralateral knee in patients with irreparable medial meniscus defect. Methods: This observational and prospective case-cohort study was conducted with patients who had irreparable meniscal defects and underwent arthroscopic meniscus scaffold implantation. Surgeries were carried out on the medial meniscus of 16 right and 4 left knees. Visual analog scale (VAS) was used to assess the degree of pain relief. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Lysholm (LYS) score were used to evaluate the functional improvement at weeks 12, 24 and 36. Concentric and eccentric quadriceps and hamstring peak torque (PT) as well as the peak torque-to-body weight (PTB) ratio, anterior–posterior, mediolateral and overall stability indexes were assessed at the same time points. Results: Twenty male patients with a mean age and body mass index of 32.2 ± 8.8 years and 26.2 ± 4.2 kg/m2, respectively, were included in the study. The amount of pain decreased from 7.6 ± 1.5% to 2.9 ± 1.5% at postoperative week 36. Range of motion, Lysholm score and KOOS increased from 87.0ο ± 9.5ο to 115.0ο ± 15.1ο, 30.8 ± 4.3 to 81.5 ± 5.3 and 37.4 ± 5.3 to 74.1 ± 7.2, respectively. Concentric quadriceps and hamstring peak torque values and peak torque/body weight ratios were improved in the knees that received a meniscus scaffold implant. Anterior/posterior, medial/lateral, and overall stability indexes with or without biofeedback exhibited a slight improvement, which was not statistically significant. Conclusion: BPMSI led to decreased pain and improved function at postoperative week 36. Although muscle strength almost returned to normal, balance parameters did not recover within 36 weeks after the procedure.