Background. Constraint-induced movement therapy (CIMT) has received considerable attention as an intervention to enhance motor recovery and cortical reorganization after stroke. Objective. The present study represents the first multi-center effort to measure cortical reorganization induced by CIMT in subjects who are in the subacute stage of recovery. Methods. A total of 30 stroke subjects in the subacute phase (>3 and <9 months poststroke) were recruited and randomized into experimental (receiving CIMT immediately after baseline evaluation) and control (receiving CIMT after 4 months) groups. Each subject was evaluated using transcranial magnetic stimulation (TMS) at baseline, 2 weeks after baseline, and at 4-month follow-up (ie, after CIMT in the experimental groups and before CIMT in the control groups). The primary clinical outcome measure was the Wolf Motor Function Test. Results. Both experimental and control groups demonstrated improved hand motor function 2 weeks after baseline. The experimental group showed significantly greater improvement in grip force after the intervention and at follow-up (P =.049). After adjusting for the baseline measures, the experimental group had an increase in the TMS motor map area compared with the control group over a 4-month period; this increase was of borderline significance (P =.053). Conclusions. Among subjects who had a stroke within the previous 3 to 9 months, CIMT produced statistically significant and clinically relevant improvements in arm motor function that persisted for at least 4 months. The corresponding enlargement of TMS motor maps, similar to that found in earlier studies of chronic stroke subjects, appears to play an important role in CIMT-dependent plasticity. Copyright © 2008 The American Society of Neurorehabilitation.