BackgroundUse of intra-articular hyaluronic acid (HA) injections to manage knee osteoarthritis (OA) remains controversial because of weak and conflicting evidence. The objective was to evaluate the effectiveness of intra-articular HA injections for knee OA management. MethodsA nested cohort of persons with knee OA seeing a specialist was created using a 10% random sample of LifeLink Plus claims (2010-2015) to compare the risk of composite (any) knee surgical interventions, total (TKA)/unicompartmental knee arthroplasty (UKA) and TKA only among HA users and 2 comparison groups: corticosteroid (CS) users and HA/CS nonusers. A high-dimensional propensity score (hdPS) was used to match HA users with CS users and with HA/CS nonusers on background covariates. The risk of surgical interventions among HA users relative to the comparison groups was assessed using Cox proportional hazard models. ResultsAmong 13,849 patients, 797 were HA users, 5327 were CS users, and 7725 were HA/CS nonusers. After hdPS matching, the risk of composite surgical interventions did not differ between HA users and HA/CS nonusers (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.67-1.16) and CS users (HR, 0.89; 95% CI, 0.65-1.12). Seven of the 8 sensitivity analyses demonstrated no significant benefit among HA users compared to CS users and HA/CS nonusers. A sensitivity analysis that restricted the study cohort to those who ultimately have knee surgery showed a lower risk of surgery of HA (HR, 0.87; 95% CI, 0.79-0.95). ConclusionThere were no significant differences in the risk of surgical interventions among HA users compared to HA/CS nonusers and CS users after accounting for residual confounding using an hdPS.