OBJECTIVES: To examine the health care resource utilization in patients with knee osteoarthritis and treated with Hylan G-F 20 (Synvisc, Genzyme Biosurgery) compared with patients treated with alternative intra-articular hyaluronic acid (HA) injections in Ontario, Canada. METHODS: This is an observational, prospective cohort of patients 18 years and older who, between June 1, 1999 and December 31, 2012 had: 1) a diagnosis of knee osteoarthritis identified by ICD 9-10 or text coding; 2) received at least 1 treatment cycle with intra-articular HA and; 3) complete pain and mobility data for each treatment cycle.  Data from the Southwestern Ontario (SWO) database, has been continuously compiled since 1999 and includes demographic, biometric, laboratory, diagnostic and health resource measures as collected in a primary care setting.  Health care resource utilization included clinic visits, emergency visits, hospitalizations, home care visits, knee bracing, radiographs, and work absenteeism. Differences between treatments were compared using independent sample t-tests. RESULTS: CONCLUSIONS: This analysis demonstrates that not all HA injections in patients with knee osteoarthritis represent similar resource utilization.  Further real world examination of the effectiveness of HA for reducing clinical symptoms and improving health care resource utilization in knee osteoarthritis is warranted.