Objectives: This study aims to compare the therapeutic effects of fixation with fibular approach, fixation with posterolateral fibular approach, and conservative therapy on supination-lateral rotation ankle fractures. Patients and methods: A total of 189 patients (103 males, 86 females; mean age: 45.7±4.7 years; range, 40 to 51 years) with supination-lateral rotation ankle fractures treated in our hospital between March 2020 and March 2021 were included in this prospective study. The patients were assigned into conservative therapy, fibular approach, and posterolateral approach groups including 63 patients in each group. Clinical conservative therapy was performed for conservative therapy group, while fibular approach and posterolateral approach groups were given fixation with fibular approach and posterolateral fibular approach, respectively. Their routine parameters, body stress, ankle function, treatment efficacy and safety were compared. Results: The length of hospital stay was shorter in the fibular approach and posterolateral approach groups than the conservative therapy group, particularly in the fibular approach group (p<0.05). The pain stress and oxidative stress were lower in the fibular approach and posterolateral approach groups than the conservative therapy group, particularly in the posterolateral approach group (p<0.05). Compared to the conservative therapy group, the fibular approach and posterolateral approach groups had significantly recovered ankle function, with better recovery in the posterolateral approach group (p<0.05). The response rate was higher in the fibular approach and posterolateral approach groups than the conservative therapy group, being higher in the posterolateral approach group (p<0.05). Conclusion: For patients with supination-lateral rotation ankle fractures, fixation with posterolateral fibular approach is more effective for expediting the recovery of ankle joints than conservative therapy and fixation with fibular approach, accompanied by higher safety.