BACKGROUND: While a number of preclinical studies have examined the effectiveness of low-intensity pulsed ultrasound (LIPUS) as a potential treatment for knee osteoarthritis (OA), there have been few clinical studies which have indirectly confirmed cartilage regeneration by magnetic resonance imaging (MRI). OBJECTIVE: The aim of this clinical trial was to investigate whether LIPUS effectively increased knee cartilage thickness and improved pain and function in knee OA patients. METHODS: This study was a prospective, single-group, home-based self-therapy trial. We included patients (n= 20) with OA pain. Each patient used an ultrasonic stimulation device (BODITREK JOINT™) for more than 20 sessions. Outcomes were assessed by MRI, Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the 36-Item Short Form Survey (SF-36) for assessing quality of life. RESULTS: Nineteen subjects completed this study. There was no significant increase in the cartilage thickness measured by MRI after LIPUS treatment. LIPUS therapy significantly decreased VAS score and WOMAC score, and significantly increased SF-36 score. The subgroup analysis in patients with knee OA showed that LIPUS treatment showed better for older patients with lower Kellgren-Lawrence grades. CONCLUSION: Pain, function, and quality of life improved after LIPUS, but there was no significant increase in cartilage thickness through MRI.