Background: Osteoarthritis (OA) is a heterogeneous disorder for which the exact cause is unknown, the condition is thought to consist of a group of overlapping distinct diseases which may occur in response to a variety of different biological and mechanical factors including metabolic, genetic or hereditary predisposition, age, physical factors such as obesity, and environmental factors. Osteoarthritis is a slowly evolving articular disease characterized by the gradual development of joint pain, stiffness and limitation of motion. Corticosteroids are commonly used in the practice of pain management for their anti-inflammatory properties. These agents, produced by the adrenal cortex, are widely used in epidural, joint, peripheral nerve and various types of soft tissue injections. The aim of the present study was to compare between the efficacy of ozone, steroid and placebo after radiofrequency ablation of genicular nerves in patient with knee osteoarthritis. Methods: This study was a Prospective, single blind randomized clinical trial study which included 75 patients suffering from pain caused by osteoarthrosis of the knee joint conducted at Benha university hospital. Results: No significant differences were reported between the study groups regarding age, gender, body mass index, pain duration, and Kellgren-Lawrence grade. The median VAS score showed an overall significant difference between the three study groups. Post hoc revealed that it was significantly higher in group I (7) than groups II (6) and III (5). No significant differences were reported between the study groups regarding VAS at baseline. No significant difference was reported between the study groups regarding oxford knee score (OKS) at baseline. No significant difference was reported between the study groups regarding global patient satisfaction. Conclusion: There was no statistically significant difference the efficacy of ozone, steroid and placebo after radiofrequency ablation of genicular nerves in patient with knee osteoarthritis.