Sixty-two patients with knee osteoarthritis (OA) were randomized to receive an intra-articular injection of corticosteroid (40 mg of triamcinolone; n=31) or oxygen-ozone (n=31) for the relief of symptoms. Outcomes of interest included pain on a visual analogue scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, range of motion, and joint effusion. Outcomes were assessed at baseline, 1 week, 1 month, and 3 months post-treatment. Results revealed a statistically significantly greater improvement in VAS pain scores (p=0.041) and WOMAC score (p=0.019) over time in the oxygen-ozone group compared to the corticosteroid group. No statistical significant differences in the improvement over time in range of motion (p=0.88) and joint effusion (p=0.369) were observed between the two groups; however, the oxygen-ozone group reported a statistically significant improvement from baseline in joint effusion at 3 months (p<0.001).