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To evaluate the effectiveness of a community-based aquatic exercise program for improved quality of life among persons with osteoarthritis.Two hundred forty-nine adults with osteoarthritis were enrolled in a 20-wk randomized controlled trial of a preexisting community-based aquatic exercise program versus control. Intervention group participants (n = 125) were asked to attend at least two aquatic exercise sessions per week. Control group participants (n = 124) were asked to maintain their usual activity levels. Demographics were collected at baseline, and patient-reported outcomes were collected at baseline and after 10 and 20 wk. Depressive symptoms, self-efficacy for pain and symptom control, physical impairment, and activity limitation were tested as potential mediators of the relationship between aquatic exercise and perceived quality of life (PQOL). Body mass index (BMI), ethnicity, self-rated health, and comorbidity were tested as possible moderators.Aquatic exercise had a positive impact on PQOL scores (P < 0.01). This effect was moderated by BMI (P < 0.05) such that benefits were observed among obese participants (BMI ≥ 30), but not among normal weight or overweight participants. None of the tested variables were found to mediate the relationship between aquatic exercise and PQOL scores.Given the availability of existing community aquatics programs, aquatic exercise offers a therapeutic and pragmatic option to promote quality of life among individuals who are living with both obesity and osteoarthritis. Future investigation is needed to replicate these findings and develop strategies to increase long-term participation in aquatics programs.