OBJECTIVE: To determine whether intraarticular glucocorticoid (GC) injections are associated with increased knee osteoarthritis (OA) progression compared to hyaluronic acid (HA) injections, which have been reported to delay OA progression and knee replacement. METHODS: We identified participants from 2 large cohort studies, the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis Study. Study visits were performed at regular intervals and included questionnaires about intraarticular GC or HA injection use in the previous 6 months and incident total knee replacement (TKR). Knee radiographs were obtained at each study visit and interpreted in a similar manner. Outcome measures were radiographic progression based on Kellgren/Lawrence (K/L) grade and joint space narrowing (JSN) for both cohorts and based on medial joint space width for OAI participants, and incident TKR. We compared preinjection and postinjection radiographs to generate rate ratios of progression comparing GC injection with HA injection. A Cox proportional hazards model was used to estimate the rate of TKR for both groups. RESULTS: We studied 791 participants (980 knees) with knee OA, of whom 629 reported GC injection use and 162 HA injection use. Rate ratios of progression were similar between those receiving GCs and those receiving HA for JSN (1.00 [95% confidence interval (95% CI) 0.83-1.21]), K/L grade (1.03 [95% CI 0.83-1.29]), and medial joint space width (1.03 [95% CI 0.72-1.48]). Hazard of TKR was slightly lower for those receiving intraarticular GC compared to those receiving HA (hazard ratio 0.75 [95% CI 0.51-1.09]). CONCLUSION: Intraarticular GC injections are not associated with an increased risk of knee OA progression compared to HA.