BACKGROUND: Many formulations and dosing regimens are available for hyaluronic acid (HA). OBJECTIVE: To compare different doses of linear, high-molecular weight (HMW) HA injections among patients with knee osteoarthritis (OA). METHODS: Hundred patients were included in this randomized, single-blinded trial and randomly divided into three HA injection groups. The first group received five weekly 20 mg HA injections, the second group received three weekly 32 mg HA injections, and the third group received a single 48 mg HA injection. Patients were evaluated at baseline, 1, 3, and 6 months after the last injection for pain, stiffness, and function using the visual analog scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Quality of life, patient’s global assessment, and Timed Up and Go (TUG) test scores were also evaluated. RESULTS: There was significant improvement in the WOMAC, VAS-pain, quality of life, patient’s global assessment, and TUG test mean scores at all follow-up time points (p< 0.001). However, the groups showed no significant differences in WOMAC, VAS-activity pain, and patient global scores at any follow-up point. CONCLUSION: Intra-articular injections of different doses of linear HMW HA can improve pain, stiffness, function, and quality of life in patients suffering from knee OA over a six-month period.