276 patients with primary knee osteoarthritis were randomized to receive either a single-shot intraarticular cross-linked hyaluronic acid (HA) injection (hyruan-one), high molecular weight HA (hylan G-F 20), or saline control. The primary outcome of interest was pain at rest and with movement on a Visual Analog Scale (VAS) after 24 weeks and a change from baseline scores. Secondary outcomes included VAS pain scores at all other time points (every 2 weeks after injection), modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. All patients had similar pain levels at 24 weeks. Pain at other time points and changes in osteoarthritis indexes were not significantly different. The hyruan-one group had a lower rate of requiring additional injections.