BACKGROUND: Osteochondral lesions of the talus (OLT) are common after ankle trauma. Studies have shown that bioactive substances, such as hyaluronic acid (HA), alone, or in combination, with surgical treatment could improve cartilage regeneration and repair, but the effect of HA on patient reported outcomes is unclear. METHODS: Literature searches were performed across four databases (PubMed, SPORTDiscus, Scopus, and The Cochrane Library) for randomized controlled trials in which at least one treatment arm involved use of HA as an adjunct to microfracture to treat patients with OLT. Primary outcomes included the American Orthopaedic Foot and Ankle Society scores (AOFAS), and the Visual Analog Scale (VAS) for pain. The level of evidence and methodological quality were evaluated using the Modified Coleman Methodology Score (MCMS). RESULTS: Three randomized studies were eligible for review with a total of 132 patients (35, 40, 57 patients, respectively) and follow-up ranged from 10.5 to 25 months. Utilization of HA at the time of microfracture resulted in greater improvement in AOFAS scores compared to microfracture alone. The pooled effect size was moderate (Standardized Mean Difference [SMD] 0.45, 95% Confidence Interval [CI] 0.06, 0.84; P = .02) and between-study heterogeneity was low (I-squared = 0%). Utilization of HA during microfracture also led to greater improvement in VAS-pain scores compared to microfracture alone. The pooled effect size was very large (SMD -3.86, 95% CI -4.75, - 2.97; P < .001) and heterogeneity was moderate (I-squared = 69%). CONCLUSION: Hyaluronic acid injection as an adjunct to arthroscopic MF in OLT provides clinically important improvements in function and pain at short-term follow-up compared to MF alone. Future longer-term follow-up studies are warranted to investigate the durability of MF with HA for treatment of OLT.