26 patients with ankle joint osteoarthritis were randomized to receive either single injections of high molecular weight hyaluronic acid (HA) (Orthovisc) at 1 mL, 2 mL, or 3 mL dosages, or 3 weekly injections of HA at a 1 mL dosage, to determine the effectiveness, safety, and dose dependency of the injections. Following 27 weeks of evaluations, results indicated that the effectiveness of hyaluronic acid injections was dose dependent. Patients who received 3 weekly injections with a dosage of 1 mL experienced a greater improvement in VAS pain scores at 7, 15, and 27 week follow-up assessments, in comparison to patients who received single injections of hyaluronic acid with 1 mL, 2 mL, or 3 mL doses. Minor adverse events were in 27% of the study population.