The standard surgical treatment for unstable ankle fractures involves open reduction and internal fixation (ORIF) with plates. However, ORIF has been associated with several complications, such as soft tissue irritation, wound infection, and nerve injury. Previous studies have shown that closed reduction and internal fixation with locked intramedullary nails (LIMNs) yields satisfactory efficacy in the treatment of ankle fractures and is associated with low complication rates. Therefore, a systematic review and meta-analysis of randomized controlled trials is imperative to provide evidence on whether or not LIMN fixation is comparable to or superior than traditional ORIF. We conducted a comprehensive literature search in the PubMed, Cochrane Library and EMBASE databases. A total of 4 randomized controlled trials involving 359 participants who suffered ankle fractures were included in this systematic review and meta-analysis. The results showed that the LIMN fixation group was statistically significant in terms of functional outcomes at the 3-month follow-up and wound-related complications. There was no statistical advantage for patients in the LIMN fixation group in terms of nonwound-related complications, total complications, or mid-term follow-up functional outcomes. There was no statistical difference between the LIMN and ORIF groups regarding operation time and quality of reduction. We believe LIMN fixation is a viable option for the treatment of unstable ankle fractures in both young and elderly individuals.Copyright © 2022 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.