Background. Intra-articular glucocorticoid injection (IAGI) is widely used for treatment of knee osteoarthritis (OA) flares. Response rates are generally around 70%. Several studies have tried to identify predictors of good response, but response to ultrasound (US)-guided injection has not yet been investigated. This study aimed to identify the predictors of response to IAGI performed under US guidance in patients with primary knee OA. Materials and methods. A total of 116 patients (116 knees) presenting with unilateral or bilateral primary knee OA were enrolled for this prospective single-center study. All were aged >40 years and met the American College of Rheumatology (ACR) criteria for knee OA. Demographic, clinical, laboratory, and imaging data were collected, injection was performed using US guidance, and tolerance was assessed. The primary efficacy endpoint was ≥40% reduction in total WOMAC score (WOMAC40). Univariate and multivariate logistic regression analyses were conducted to identify the predictors of response. Results. The mean age of the patients was 64.2 ± 9.4 years and mean BMI was 29.9 ± 3.8 kg/m2. Total WOMAC40 response rate was 61.2%. In multivariate analysis, the independent predictors of response were BMI <30 kg/m2 (OR = 0.38 [0.16 – 0.89], p = 0.025) and ESR <20 mm (OR = 0.27 [0.08 – 0, 90], p = 0.033). Conclusion. Knee OA patients with BMI <30 kg/m2 and/or ESR <20 mm have higher chance of having satisfactory response to US-guided IAGI. Clinical and radiographic severity and age do not seem to affect the probability of response.