Objective : We performed a systematic review to investigate improvements in body function and structure, activity, and health-related quality of life from exercise programs of >150 days' duration in patients with knee osteoarthritis (OA). Methods : We collected data on randomized controlled trials (RCTs) comparing the effects of exercise intervention with those of either nonintervention or psychoeducational intervention in patients with knee OA. Data were collected on pain, stiffness, muscle strength, range of motion, flexibility, maximal oxygen uptake, proprioception, time to climb a flight of stairs, disability as assessed by the Western Ontario and McMaster Universities Arthritis Index (WOMAC), walking distance (e.g., 6-min walking-distance test), walking time (e.g., time to walk arbitrary distances), walking velocity, and health-related quality of life assessed using the SF-36^® Health Survey (SF-36). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to determine the quality of the evidence. Results: Forty-one RCTs were identified. Outcomes that were significantly affected by exercise programs of >150 days were knee flexion muscle strength at a functional level, time to climb a flight of stairs and walking distance at activity level, and SF-36 General Health, Physical Functioning, Role-Physical, and Bodily Pain scales. The quality of evidence for these outcomes was moderate to high. Conclusion : In patients with knee OA, improvements in body function, activity, and health-related quality of life can be maintained with exercise programs of >150 days' duration, and these findings are supported by a moderate to high level of evidence.