Limited studies are available in management of primary osteoarthritis of knee with prolotherapy with 25% dextrose and ozone therapy. A randomized controlled trial was conducted to study the effectiveness of 25% dextrose prolotherapy and ozone therapy in primary osteoarthritis of knee in terms of pain and improvement of knee function in sixty–six patients in age group of 50 to 70 yrs attending PMR department, RIMS, Imphal. The study group received of 25% dextrose 6 ml, 3 times at baseline, at 1 month and 6 month and the control group received 15 ml of ozone intra– articularly. In both the groups 50 mg of tramadol tablet and isometric strengthening exercise of quadriceps was given. Assessment was done at baseline, at 1 month and 6 months in terms of VAS and WOMAC. Statistically significant improvement was noted in VAS (7.48±0.91 to 1.94±0.70) and WOMAC score (83.21±3.66 to 15.24±2.25) at 6 month follow up in control group. Significant difference was also noted in VAS (7.27±1.10to 3.24±1.09) and WOMAC score (79.33±16.67 to 28.42±11.55) among study group.    It was concluded that Ozone therapy was more effective than dextrose prolotherapy in management of primary osteoarthritis of knee.