Osteoarthritis (OA) is the most common form of arthritis and some joints are effected more than others. The prevalence of OA increases with age and it represents the major problem for functional impairment in older patients. Non-surgical treatment with oral drugs is not suitable for many patients suffering from gastric disorders, high blood pressure or different heart diseases. Intra-articular injections are a promising solution in these cases. This study was performed to compare the efficacy and safety of ozone injections, PRP (platelet rich plasma) injections and combined ozone plus PRP injections in patients with symptomatic knee OA. 120 patients were diagnosed of OA according to the criteria of the American College of Rheumatology and included into this study. Patients were randomly divided into three equal groups (40 patients each group). We include patients whose VAS score was 5 or above. Patients with inflammatory, endocrine and metabolic disturbances, and patients who had meniscectomy within the past 10 years, extra articular surgery within the last year, arthrocentesis in last 6 months or any drug given intra-articular were not included. We did not include either patients with misalignment. Patients in the first group were treated with intra-articular injections of ozone/oxygen gas mixture 2 times/week, at 10 µg/mL concentration and a volume of 5 mL for a total of 12 injections. Patients in the second group were treated only with PRP injections once a week for a total of 3 times. Patients in the third group were treated with intra-articular injections of Ozone+PRP (10 µg/ml concentration, 5 ml volume) once a week for a total of 3 times. The pain levels of patients were measured with Visual Analog Scale (VAS). Side effects were collected using an open list record. All the groups improved their baseline VAS in a significant way, although the group with the best results was group 3 with the combination of ozone and PRP in the same injection. We are planning further studies including systemic ozone in order to improve more the pain in our patients.