132 patients with mild-to-moderate, symptomatic knee osteoarthritis were randomized to a single injection of either HYA-JOINT Plus (SciVision Biotech) or Synvisc-One (Sanofi-Aventis). Patients were assessed over a 6-month follow-up for patient-reported outcome measures, functional performance measures, patient satisfaction, and rate of adverse events. Pain assessed using a visual analog scale was significantly lower in the HYA-JOINT Plus group compared to the Synvisc-One group at 1, 3, and 6 months, but pain assessed on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) did not significantly differ between groups at any point. WOMAC Stiffness score at 6 months was also significantly lower in the HYA-JOINT Plus group compared to the Synvisc-One group. All other outcomes demonstrated no significant differences between groups over the duration of follow-up.