Limited studies are available in management of primary osteoarthritis of knee with prolotherapy with 25% dextrose and methyl prednisolone. A prospective comparative study was conducted to see the effectiveness of 25% dextrose prolotherapy and methyl prednisolone 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 first group received 6 ml injections of 25% dextrose, 3 times at baseline, 1^st month and 4^th month and the second group received single dose of 80 mg of methyl prednisolone 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^st, 4^th and 8^th months by VAS and WOMAC. Statistically significant improvement was noted in VAS (5.91±0.82       to2.65±0.94) and WOMAC score (45.25±6.68 to 20.25±7.67) at end of 8^th month in first group. It was concluded that 25% dextrose was more effective than in management of primary osteoarthritis of knee.