126 patients with knee osteoarthritis (OA) and at least one comorbid disease (cardiac disease, heart failure, diabetes, chronic obstructive pulmonary disease, or obesity) were randomized to receive either specialized exercise therapy or placed on a waiting list. The purpose of this study was to determine the effectiveness and safety of an exercise therapy treatment when compared to a control group. Findings indicated significantly greater scores for WOMAC, six-minute walk test, get up and go test, stair climbing test, muscle strength, and joint pain compared to the control group after 32 weeks of assessment. No adverse events occurred during the intervention.