To investigate the effect of anterior cruciate ligament (ACL) integrity on the short- and mid-term effectiveness of mobile-bearing medial unicompartmental knee arthroplasty (UKA). The clinical data of 128 patients with anteromedial osteoarthritis who underwent mobile-bearing medial UKA between June 2019 and June 2021 was retrospectively analyzed. According to the integrity of ACL structure under direct vision during operation, the patients were divided into normal group (30 cases), synovial defect group (53 cases), and longitudinal split group (45 cases). There was no significant difference in gender, age, body mass index, preoperative knee range of motion (ROM), hip-knee-ankle angle (HKA), Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and other baseline data among the 3 groups ( P>0.05). The knee ROM, KSS score (including clinical and functional scores), WOMAC score (including pain, stiffness, and function scores) before operation and at last follow-up, the Lysholm score, International Knee Documentation Committee (IKDC) score, and Forgetting Joint Score (FJS-12) at last follow-up were recorded and compared among the 3 groups. Imaging examination was performed to evaluate the wear of cartilage in the lateral tibiofemoral compartment and patellofemoral compartment of the knee joint. HKA and posterior tibial slope (PTS) were measured at last follow-up. All the patients of 3 groups were followed up 22-56 months (mean, 40.4 months). There was no significant difference in follow-up time among the 3 groups ( P>0.05). At last follow-up, imaging examination showed no obvious cartilage wear progression of the lateral tibiofemoral compartment and patellofemoral compartment, and no adverse events such as aseptic loosening of the prosthesis, dislocation of the removable pad, or infection occurred during the follow-up. At last follow-up, knee ROM, HKA, KSS scores, and WOMAC scores of the 3 groups significantly improved when compared with preoperative ones ( P<0.05). There was no significant difference in the changes of the above indicators before and after operation, and also the Lysholm score, IKDC score, FJS-12 score, and PTS among the 3 groups ( P>0.05). The integrity of ACL has no significant effect on the short- and mid-term effectiveness of mobile-bearing medial UKA.