Objective. To determine, at 6 weeks postsurgery, if a monitored home exercise program (HEP) is not inferior to usual care rehabilitation for patients undergoing primary unilateral total knee replacement (TKR) surgery for osteoarthritis. Methods. We conducted a multicenter, randomized clinical trial. Patients ages 45-75 years were allocated at the time of hospital discharge to usual care rehabilitation (n ؍ 196) or the HEP (n ؍ 194). Outcomes assessed 6 weeks after surgery included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscales, knee range of motion, and the 50-foot walk time. The upper bound of the 95% confidence interval (95% CI) mean difference favoring usual care was used to determine noninferiority. Results. At 6 weeks after surgery there were no significant differences between usual care and HEP, respectively, for pain (7.4 and 7.2; 95% CI mean difference [MD] ؊0.7, 0.9), physical function (22.5 and 22.4; 95% CI MD ؊2.5, 2.6), knee flexion (96°and 97°; 95% CI MD ؊4°, 2°), knee extension (؊7°and ؊6°; 95% CI MD ؊2°, 1°), or the 50-foot walk time (12.9 and 12.9 seconds; 95% CI MD ؊0.8, 0.7 seconds). At 6 weeks, 18 patients (9%) allocated to usual care and 11 (6%) to the HEP did not achieve 80°knee flexion. There was no difference between the treatment allocations in the number of hospital readmissions. Conclusion. The HEP was not inferior to usual care as an early rehabilitation protocol after primary TKR.