OBJECTIVE: The purpose of this study was to compare the effectiveness of three injections of standard linear HA versus single injection of lightly cross-linking HA in patients with knee OA. METHODS: Forty subjects were randomized into two groups. The first group received single dose intraarticular injection of 4 ml lightly cross-linking sodium hyaluronate (Monovisc), and the second group received three consecutive intraarticular injections of 2.5 ml standard linear sodium hyaluronate (Adant) with one week intervals. Visual analog scale (VAS)-pain and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores were measured. RESULTS: In both groups, VAS-pain and WOMAC scores (except WOMAC-stiffness) were improved statistically lasting up to the 6th month with respect to before injection values (p< 0.001). There were no statistical differences in VAS-pain and WOMAC scores after injections (p> 0.05) in both groups. But in the 6th month visit, VAS-resting values were found to be statistically improved in standard linear HA group compared to lightly cross-linking HA group (p< 0.05). CONCLUSION: Although three-dose administration was significantly superior to single-dose at the sixth month, current knowledge is not sufficient to decide whether single-dose or multiple-dose HA injection should be chosen. There is a clear need for verification of our results with long-term studies on larger patient groups.