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Purpose: Osteochondral lesions of the talus are often located posteromedially requiring open surgery to facilitate solid and complete osteochondral reconstruction. The aim of the study was to identify the optimal anatomical site for medial malleolar osteotomy based on the criteria of minimal cartilage damage (Study I) and to report on the morbidity in patients receiving osteotomy performed at the previously identified site (Study II)., Methods: For Study I, cartilage coverage of the tibiofibular ankle joint facet was measured in 40 cadaveric ankles (20 cadaver specimens). In Study II, we assessed clinical (VAS pain score, AOFAS score, range of motion) and radiological outcome measures (SPECT-CT) in 17 patients (mean age, 36.8 ± 10.8 years) undergoing medial malleolar osteotomy., Results: The medial edge in the transition zone of the tibial plafond to the medial malleolus showed less than 75 % of cartilage coverage in 62.5 % of cadavers (Study I). Surgery resulted in lower pain levels (2.4 ± 2.6 compared with 6.3 ± 1.8 points; p < 0.001) and greater AOFAS scores (82.9 ± 14.1 compared with 43.5 ± 10.8 to points; p < 0.001) compared with baseline (Study II). No signs of intra-operative damage or mal- or non-union were found. Long-term morbidity was found in one patient. Implant removal was necessary in 12 of 17 patients (71 %)., Conclusion: Anatomically, there is an optimal location for the medial malleolar osteotomy at the medial ankle edge involving minimal cartilage damage. Clinical results using this location showed no short- or mid-term morbidity and little long-term morbidity. However, many patients required re-intervention for implant removal., Level of Evidence: IV.