BACKGROUND: The effectiveness of glucosamine sulfate as a symptom and disease modifier for osteoarthritis is still under debate. OBJECTIVE: To assess whether glucosamine sulfate has an effect on the symptoms and structural progression of hip osteoarthritis during 2 years of treatment. DESIGN: Randomized, controlled trial. SETTING: Primary care in the Netherlands. PATIENTS: 222 patients with hip osteoarthritis who were recruited by their general practitioner. Patients were eligible if they met the American College of Rheumatology clinical criteria for hip osteoarthritis. INTERVENTION: 2 years of treatment with 1500 mg of oral glucosamine sulfate or placebo once daily. MEASUREMENTS: Primary outcome measures were Western Ontario and McMaster Universities (WOMAC) pain and function subscales over 24 months and joint space narrowing after 24 months. The main secondary outcome measures were WOMAC pain, function, and stiffness after 3, 12, and 24 months. RESULTS: At baseline, both groups were similar in demographic and clinical variables. Overall, WOMAC pain did not differ (mean difference [glucosamine sulfate minus placebo], -1.54 [95% CI, -5.43 to 2.36]), nor did WOMAC function (mean difference, -2.01 [CI, -5.38 to 1.36]). Joint space narrowing also did not differ after 24 months (mean difference, -0.029 [CI, -0.122 to 0.064]). Only 1 of the sensitivity analyses, based on extreme assumptions regarding missing assessments due to total hip replacement, provided results consistent with a glucosamine effect. LIMITATIONS: Twenty patients had total hip replacement during the trial. Half of the patients had a Kellgren and Lawrence score of 1. CONCLUSION: Glucosamine sulfate was no better than placebo in reducing symptoms and progression of hip osteoarthritis. International Standard Randomised Controlled Trial Number: ISRCTN54513166.