Background: Flexible ligamentous fixation has increased in popularity for the treatment of ligamentous Lisfranc injury, but the optimal fixation strategy is unclear. Purpose: To review the biomechanical, clinical, and radiographic results of ligamentous Lisfranc injuries treated with flexible fixation. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic literature review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed/Medline and Google Scholar literature databases were queried for clinical and biomechanical (cadaveric) studies relating to flexible fixation of ligamentous Lisfranc injury. Outcomes of interest included patient-reported outcome scores, clinical/biomechanical results, radiographic alignment, and return to activity. Where appropriate, meta-analysis of the postoperative outcomes was performed. Results: Of the 34 initial studies, 14 articles (243 feet) were included in the analysis. In the 11 clinical studies (216 patients), the mean postoperative American Orthopaedic Foot & Ankle Society score was 90.1 (n = 150; 6 studies) and the mean visual analog scale score was 1.5 (n = 137; 5 studies). The rate of return to activity was 100% (n = 35; 5 studies), and 100% of patients maintained radiographic alignment postoperatively (n = 62; 6 studies). No complications or subsequent hardware removals were reported. Of the 3 biomechanical studies (27 feet), 1 study found significantly greater change in diastasis under axial load between intact and postfixation ligaments with suture button versus screw fixation (+1.1 vs –0.1 mm; P < .05), another found no difference in the decrease in diastasis under axial load between the injured state and screw or suture button fixation (1.2 vs 1.0 mm; P = .5), and the third found no difference in displacement between intact and either screw or suture button fixation under either axial (intact vs screw: 1.0 vs 2.0 mm, P = .1; intact vs suture button: 0.6 vs 1.8 mm, P = .1) or abduction (intact vs screw: 1.5 vs 1.1 mm, P = .5; intact vs suture button: 1.3 vs 2.1 mm, P = .1) load. Conclusion: Flexible fixation use in the treatment of ligamentous Lisfranc injury was found to have significant potential as a fixation option, as demonstrated by excellent clinical results. Biomechanical evidence was inconclusive but suggested a trend toward decreased diastasis in specimens fixed with screws compared with suture buttons.