OBJECTIVE: Knee osteoarthritis (OA) is a commonly undiagnosed condition and care is often not provided. Pharmacists are uniquely placed for launching a multidisciplinary intervention for knee OA. METHODS: We performed a cluster randomized controlled trial with pharmacies providing either intervention care or usual care (14 and 18 pharmacies, respectively). The intervention included a validated knee OA screening questionnaire, education, pain medication management, physiotherapy-guided exercise, and communication with the primary care physician. Usual care consisted of an educational pamphlet. The primary outcome was the pass rate on the Arthritis Foundation's quality indicators for OA. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Lower Extremity Function Scale (LEFS), the Paper Adaptive Test-5D (PAT-5D), and the Health Utilities Index Mark 3 (HUI3). RESULTS: One hundred thirty-nine patients were assigned to the control (n = 66) and intervention (n = 73) groups. There were no differences between the groups in baseline measures. The overall quality indicator pass rate was significantly higher in the intervention arm compared to the control arm (difference of 45.2%; 95% confidence interval 34.5, 55.9). Significant improvements were observed for the intervention care group as compared to the usual care group in the WOMAC global, pain, and function scores at 3 and 6 months (all P < 0.01); the PAT-5D daily activity scores at 3 and 6 months (both P < 0.05); the PAT-5D pain scores at 6 months (P = 0.05); the HUI3 single-attribute pain scores at 3 and 6 months (all P < 0.05); and the LEFS scores at 6 months (P < 0.05). CONCLUSION: Pharmacists can launch a multidisciplinary intervention to identify knee OA cases, improve the utilization of treatments, and improve function, pain, and quality of life.