514 patients with knee osteoarthritis were randomized to one of three groups for exercise therapy: usual care, which included advice and prescription of exercises over 4 sessions with a physiotherapist; an individually tailored lower-limb exercise therapy program over 12 weeks; and a targeted exercise adherence program, which focused on transitioning patients from lower-limb exercises to an increase in overall activity level over 6 months. Pain and function scores were recorded from 3 to 18 months after randomization, and cost-effectiveness after 18 months was evaluated. Results demonstrated no significant differences between groups in pain or function scores throughout follow-up. Usual care demonstrated the lowest costs with higher quality-adjusted life years (QALYs).