Introduction: The purpose of this study was to evaluate clinical and biochemical efficacy of autologous intraarticular (IA) platelet rich plasma (PRP) compared to saline and to measure effectiveness of single and multiple doses given at monthly intervals for Kellgren-Lawrence (K-L) grade II, III knee osteoarthritis (KOA). Materials and methods: A total of 130 patients were randomised into 4 groups; PRP-1 (n=36), PRP-2 (n=34), PRP-3 (n=32) and saline (NS) (n=28), after approval from institute ethics committee (reference number: TMU/IEC/20- 21/091) and was conducted in accordance with Helsinki declaration. Groups PRP-1, PRP-2, PRP-3 received single, double and triple injections of PRP whereas NS group received single saline (0.9%) injection. Assessment of outcome scores (visual analogue scale [VAS] and Western Ontario and McMaster Universities Arthritis Index [WOMAC]) was done at baseline and three, six, nine months post intervention. Serum collagen 2-1 (Coll2-1) estimation at baseline and nine months post-therapy was used for biochemical assessment. Results: Improvement in VAS and WOMAC was statistically significant and clinically meaningful (Minimal clinically important change [MCIC]; >12% of baseline and ≥2cm difference in mean for WOMAC and VAS, respectively) for groups PRP-1, PRP-2 and PRP-3 in comparison to saline (P<0.05), at every follow-up. PRP groups also exhibited a significant decrease in serum Coll2- 1 at 9 months (P<0.05). On comparison among the PRP groups, multiple doses (groups PRP-2 and PRP-3) produced significantly better clinical results than single dose (group PRP-1) (P<0.05), whereas the difference in Coll2-1 levels was significant for group PRP-1 vs PRP-3 only (P<0.05). Conclusion: PRP results in clinically significant amelioration of functional and pain scores as well as significant reduction in serum levels of Coll2-1 in K-L grade II, III KOA over nine months. These benefits can be accentuated by multiple doses given one month apart.