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Subchondral bone marrow edema (BME) has been associated with articular cartilage loss, with the potential to be a negative prognostic indicator for clinical outcomes after microfracture. However, no single study has investigated the association between BME and clinical outcomes after microfracture for osteochondral lesions of the talus (OLTs) at midterm follow-up.To clarify the association between postoperative subchondral BME and clinical outcomes in patients treated with microfracture for OLTs at both short-term and midterm follow-up using a grading system that classified the extent of BME of the talus.Cohort study; Level of evidence, 3.Patients who underwent microfracture between 2008 and 2013 were assessed at 2- and 4-year postoperative follow-up. BME was evaluated using magnetic resonance imaging, and the presence of subchondral BME was determined with fat-suppressed T2-weighted sequences. Clinical outcomes were evaluated using the Foot and Ankle Outcome Score (FAOS). P < .05 was considered to be statistically significant.Forty-three (83%) of 52 eligible patients were included. No significant differences were found in the FAOS between the BME and no BME groups at 2-year follow-up (83.1 ± 6.5 vs 88.6 ± 8.0, respectively; P = .109), but there was a significant difference at 4-year follow-up (77.5 ± 11.1 vs 84.7 ± 8.4, respectively; P = .041). A significant difference was found among BME grades at 4-year follow-up (grade 0: 84.7 ± 7.4, grade 1: 80.1 ± 10.5, grade 2: 74.0 ± 10.3, and grade 3: 67.5 ± 7.1; P = .035). A post hoc analysis showed significant differences between grades 0 and 2, 0 and 3, and 1 and 3 (P = .041, .037, and .048, respectively). In addition, at 4-year follow-up, a significant correlation was noted between the FAOS and BME grade (r = −0.453, P = .003) but not at 2-year follow-up (r = −0.212, P = .178). Seventy-four percent of patients still had subchondral BME at 4-year follow-up after microfracture for OLTs.Patients with subchondral BME at midterm follow-up after microfracture for OLTs had worse clinical outcomes than those without subchondral BME. In addition, the degree of subchondral BME at midterm follow-up was correlated with clinical outcomes. However, at short-term follow-up, there were no significant differences in clinical outcomes based on both the presence and degree of BME, and no correlation was found between clinical outcomes and the degree of BME. The current study suggests that BME at short-term follow-up is a normal physiological reaction. However, BME at midterm follow-up after microfracture for OLTs may be pathological and is associated with poorer clinical outcomes.