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To describe the clinical course of knee osteoarthritis following a single course of intra-articular hyaluronic acid (HA) injection clinic, and specifically to explore treatment withdrawal.Prospective consecutive case series with follow-up, set in an innovative physiotherapistled clinic, based in a hospital orthopaedic surgery department. Participants: A total of 100 patients with knee osteoarthritis referred to the clinic received a single course of five injections of Hyalgan®. Patients were followed up in clinic at five, 13, 26 and 52 weeks. The primary outcome measures were Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) Likert 3.0 pain (0–20) and physical function (0–68) scores. In addition, at 13 and 26 weeks, patients were reviewed independently by an orthopaedic surgeon, with the option of withdrawing for alternative management those patients who had not responded.Ninety (90%) patients were successfully followed to study endpoint. Improvements were seen at five weeks and, to a lesser extent, at 13 weeks (mean reduction in WOMAC pain at 13 weeks 1.3; 95% confidence interval [CI] 0.5, 2.0; mean reduction in WOMAC Physical Function at 13 weeks 5.6; 95% CI 3.0, 8.1). Of 34 treatment withdrawals, most had returned to baseline levels by 13 weeks. The remaining 56 patients maintained improvements up to 52 weeks, although the pattern of outcome was highly variable between individuals. Withdrawals and non-responders had higher initial pain severity.Physiotherapist-led intra-articular HA clinics are feasible. Clinical outcomes for individual patients are highly heterogeneous up to one year after injections. Patients with initially high levels of pain may be less likely to benefit. Copyright © 2008 John Wiley & Sons, Ltd.