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Objective: To evaluate the effect of preventive interventions for lateral ankle sprain in the general population., Data Sources: A search of PubMed, EMBASE, Cochrane CENTRAL, Medline, CINAHL, and ClinicalTrials.gov was conducted up to August 2022., Review Methods: Randomized controlled trials and prospective cohort studies that evaluated any interventions for preventing lateral ankle sprain were included. Two reviewers independently conducted the search, screening, and data extraction. The methodological quality of each study was assessed using the revised Cochrane risk-of-bias tool for randomized trials or using the Cochrane Risk Of Bias In Non-Randomized Studies tool for prospective cohort studies., Results: Seventeen studies met the inclusion criteria. Proprioceptive training exhibited better effects on preventing future lateral ankle sprain compared with the control group (risk ratio = 0.59, p < 0.001), and a stronger preventive effect was observed in participants with a history of lateral ankle sprain in the subgroup analysis (risk ratio = 0.49, p = 0.02). Compared with no bracing, ankle bracing had no significant better effect in preventing lateral ankle sprain (risk ratio = 0.43, p = 0.05). Proprioceptive training and ankle bracing had similar preventive effects (risk ratio = 0.98, p = 0.97). Limited evidence hindered the synthesis of data on pain, swelling, costs, and time loss., Conclusion: Proprioceptive training is recommended for preventing lateral ankle sprain, especially for people with a history of lateral ankle sprain. Bracing seems to have an ambiguous preventive effect and requires more further investigation.