BACKGROUND AND PURPOSE: Constraint-Induced Movement therapy (CI therapy) is a neurorehabilitation technique developed to improve use of the more affected upper extremity after stroke. A number of studies have reported positive effects for this intervention, but an experiment with a credible placebo control group has not yet been published. METHODS: We conducted a placebo-controlled trial of CI therapy in patients with mild to moderate chronic (mean=4.5 years after stroke) motor deficit after stroke. The CI therapy group received intensive training (shaping) of the more affected upper extremity for 6 hours per day on 10 consecutive weekdays, restraint of the less affected extremity for a target of 90% of waking hours during the 2-week treatment period, and application of a number of other techniques designed to produce transfer to the life situation. The placebo group received a program of physical fitness, cognitive, and relaxation exercises for the same length of time and with the same amount of therapist interaction as the experimental group. RESULTS: After CI therapy, patients showed large (Wolf Motor Function Test) to very large improvements in the functional use of their more affected arm in their daily lives (Motor Activity Log; P<0.0001). The changes persisted over the 2 years tested. Placebo subjects showed no significant changes. CONCLUSIONS: The results support the efficacy of CI therapy for rehabilitating upper extremity motor function in patients with chronic stroke.