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Objective: To determine the analgesic efficacy of ozone gas versus hyaluronic acid solution in knee osteoarthritis patients. Study Design: Quasi-experimental study. Place and duration of study: Department of Pain Medicine, Combined Military Hospital, Rawalpindi Pakistan, from Jun to Dec 2020. Methodology: Seventy patients suffering from knee osteoarthritis fulfilling the inclusion criteria were included in this study and were randomly assigned to two equal groups to undergo intra-articular knee injection using either Hyaluronic Acid (Group-H) or Ozone (Group-O). Improvement in the numeric rating scale (NRS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale were recorded 1, 3 and 6 months after the procedure. Results: In both groups, the pain score (Group-H Pre-procedure NRS =7.66±0.87 vs. Post-Procedure 6 month NRS = 4.74±0.70, Group-O Pre-procedure NRS = 7.86±0.88 vs. Post-Procedure 6 month NRS = 4.46±0.92) and WOMAC (Group-H Pre-procedure =77.60±7.93 vs. Post-Procedure 6 month =40.31±6.81, Group-O Pre-procedure=75.54±9.40 vs. Post-Procedure 6 month =38.37±8.98) score improved. However, the NRS pain score (p-value = 0.21) and patient WOMAC score (p-value = 0.31) were not significantly different between groups. Conclusion: Neither Hyaluronic Acid nor Ozone appears superior in decreasing pain scores or physical limitations, particularly for knee osteoarthritis. [ABSTRACT FROM AUTHOR]