BACKGROUND: Intra-articular corticosteroid injection is commonly used for pain relief in ankle osteoarthritis (OA). The effects of corticosteroids (CS) are short-lived, whereas hyaluronic acid (HA) have longer-lasting effects. The objective was to compare the efficacy of dual injections of CS and HA to CS alone. We hypothesized that intra-articular injections of dual agents would be more effective than CS alone. METHODS: A single-blind, randomized, controlled trial was designed to investigate this hypothesis. 135 patients with ankle OA were enrolled into an intra-articular CS injection group (CS group, n = 61) or dual HA plus CS injection group (CS + HA group, n = 74). The CS group received 1 mL of corticosteroid and 1 mL of 0.5% bupivacaine and 1 mL of normal saline once, and the CS + HA group received 3 mL of a total of 5 mL mixtures containing 2 mL of HA, or 1 mL of corticosteroid, 0.5% bupivacaine, and normal saline in the first week, followed by 2 mL of HA in the second and third weeks. Clinical evaluations were performed before injection, 6 and 12 weeks after the first injections. The Ankle Osteoarthritis Scale (AOS) was used as the primary outcome measure, and the Visual Analogue Scale (VAS), Short Form Health Survey (SF-36), and complications were used as secondary outcomes. RESULTS: The mean AOS change from baseline was significantly greater in the CS + HA group than in the CS group at 6 (p ≤ 0.01) and 12 weeks (p ≤ 0.01). The mean VAS change from baseline was significantly greater in the CS group than in the CS + HA group at 6 weeks (p = 0.023), but not at 12 weeks (p = 0.731). The mean SF-36 change from baseline was not significant between the CS and CS + HA groups at 6 (p = 0.416) and 12 weeks (p = 0.215). CONCLUSIONS: The combination of corticosteroid and HA injection is more effective than corticosteroid alone in relieving pain in ankle OA. TRIAL REGISTRATION: Clinical Research Information Service in South Korea, KCT0008690 // Registration Date (First Posted): July 21th, 2023 ( http://cris.nih.go.kr ).