The objective of this study was to compare the efficacy of low molecular weight intra-articular hyaluronic acid (LMW IA-HA,1.4X106 Dalton) and high molecular weight intraarticular hyaluronic acid (HMW IA-HA 6X106 Dalton) in the rigkt/left knee of each patient. A prospective, randomized, single blind clinical trial was conducted in patients with primary OA of both knees and radiographic changes to Kellgren & Lawrence stage II or III bilaterally. Each patient received both drugs, only one drug to one knee, by simple randomization and the study was conducted for 17 weeks. Thirty two patients were enrolled in the study; one group of 32 knees received LMW IA-HA and the other group of 32 knees received HMW IA-HA. At the end of the study, the total WOMAC scores decreased significantly in both LMW and HMW IA-Has treated knees (p<0.001). However, there was no significant difference of the total WOMAC scores between both groups (p=0.689). Both of the patient and physician global assessments showed that HMW IA-HA treated knee group had a significant lower score (p<0.001). The most frequently detected adverse drug reaction (ADR) was transient pain at the injection site and no serious ADR was reported.