Background: We aimed to compare midterm radiological and clinical outcomes between closed reduction and internal fixation (CRIF) using the fibular intramedullary nail (IMN) and open reduction and internal fixation (ORIF) using the locking plate for the treatment of unstable ankle fractures in active young patients. Methods: In this retrospective cohort study, 204 patients treated with CRIF using the fibular IMN (94 patients) or ORIF using the locking plate (110 patients) were included after at least 3 years of follow-up. The mean patient age was 41.4 years. Radiographic evaluation included the quality of reduction assessed by plain radiography and 3-dimensional (3D)–reconstructed computed tomography as well as the development of posttraumatic osteoarthritis (PTOA) of the ankle assessed by weightbearing plain radiography. Clinical evaluation included the American Orthopaedic Foot & Ankle Society hindfoot score, Olerud and Molander Score, the Foot and Ankle Outcome Score, and visual analog scale pain score as well as complications. Results: At median follow-up greater than 4 years, we found no significant differences in measured clinical outcomes between the 2 groups. There were significantly fewer postoperative complications in the IMN group than in the ORIF group (9.5% vs 39%, P < .001). However, we did find a greater proportion of radiographically fair or poor reductions in the IMN group than in the ORIF group ( P < .001). The poor reductions in the IMN group were primarily related to Weber type C, pronation-type injury, and comminuted fibular and trimalleolar fractures ( P < .001). PTOA was also more frequently observed in the IMN group than in the ORIF group (21.3% vs 9.1%, P = .024). Conclusion: Given the current prevailing technologies for fracture fixation, this study suggests that surgeons should consider ORIF for unstable ankle fractures in active young patients with Weber type C, pronation-type injury, and comminuted fibular and trimalleolar fractures. Level of Evidence: Level III, retrospective comparative study.