© 2018, © The Author(s) 2018. Background. Constraint-Induced Movement therapy (CIMT) has controlled evidence of efficacy for improving real-world paretic limb use in non-progressive physically disabling disorders (stroke, cerebral palsy). Objective. This study sought to determine whether this therapy can produce comparable results with a progressive disorder such as multiple sclerosis (MS). We conducted a preliminary phase II randomized controlled trial of CIMT versus a program of complementary and alternative medicine (CAM) treatments for persons with MS, to evaluate their effect on real-world disability. Methods. Twenty adults with hemiparetic MS underwent 35 hours of either CIMT or CAM over 10 consecutive weekdays. The primary clinical outcome was change from pretreatment on the Motor Activity Log (MAL). Results. The CIMT group improved more on the MAL (2.7 points, 95% confidence interval 2.2-3.2) than did the CAM group (0.5 points, 95% confidence interval −0.1 to 1.1; P <.001). These results did not change at 1-year follow-up, indicating long-term retention of functional benefit for CIMT. The treatments were well tolerated and without adverse events. Conclusion. These results suggest that CIMT can increase real-world use of the more-affected arm in patients with MS for at least 1 year. Clinical Trial Registration. ClinicalTrials.gov NCT01081275.