120 patients with Kellgren-Lawrence grade II-III knee osteoarthritis were randomized to one of three intra-articular injection groups: platelet rich plasma, hyaluronic acid, or ozone. The purpose of this study was to compare visual analog scores (VAS) for pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for pain, stiffness, and function over a 12-month follow-up. The results demonstrated a marked decrease in all outcome measures within the first month in all three groups, followed by a regression at subsequent follow-ups. Between-group differences were identified, with lower scores generally observed in the PRP and HA groups compared to the ozone group at 1, 3, and 6 months. By 12 months, scores in the ozone group had returned to baseline, while scores in the PRP and HA groups were lower, relatively. Also at 12 months, differences were found between the PRP and HA groups for outcome scores, favouring the PPR group.