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Category: Ankle; Hindfoot; Sports Introduction/Purpose: Autologous matrix-induced chondrogenesis (AMIC) has shown to result in favorable clinical outcome in patients with osteochondral lesions of the talus (OLT). Yet, the influence of ankle instability on cartilage repair of the ankle has still to be determined. This study sought to compare the clinical and radiographic outcome in patients with and without concomitant lateral ligament stabilization (LLS) undergoing AMIC for the treatment of OLT. Methods: This study evaluated AMIC that were implanted in patients for the treatment of symptomatic OLT with and without concomitant ankle instability. Postoperative MRI, Tegner, AOFAS and Cumberland Ankle Instability Tool (CAIT) were obtained at a minimum follow-up of 2 years. A musculoskeletal radiologist scored all grafts according to the MOCART 1 and 2.0 scores. Patients were stratified into two groups based on whether they underwent concomitant LLS for ankle instability. Patients without LLS served as controls. Patients were matched 1:1 for BMI, lesion size, follow-up and age. Results: Twenty-six patients that underwent AMIC with a mean follow-up of 4.2 +- 1.5 years were enrolled in this study (13 with and 13 without concomitant ankle instability). Patients' mean age was 33.4 +- 12.7 years with a BMI averaging 26.2 +- 3.7. Patients with concomitant LLS showed worse clinical outcome measured by AOFAS (85.1 +- 14.4 vs. 96.3 +- 5.8, p=0.034) and Tegner (3.8 +- 1.1 vs. 4.4 +- 2.3, p=0.012). No difference was seen between both groups regarding MOCART 1 and 2.0 scores (p=0.714 and p=0.371, respectively). Additionally, postoperative CAIT and AOFAS significantly correlated in patients that underwent concomitant LLS (r=0.766, p=0.002) with a CAIT score of > 24 (stable ankle joint) resulting in AOFAS scores comparable to scores in patients with isolated AMIC (90.1 +- 11.6 vs. 95.3 +- 6.6; p=0.442). Conclusion: The results of this study suggest a negative influence of ankle instability on the clinical outcome of cartilage repair with AMIC for the treatment of OLT. If postoperative ankle stability is achieved in patients with LLS, however, comparable outcome as seen after isolated AMIC can be expected.