OBJECTIVE: To quantify the preventive effect of a neutral functional realignment orthosis on pain, mobility, and edema of the hand in subacute hemiparetic poststroke patients with severe motor deficits. DESIGN: Randomized trial. SETTING: Rehabilitation center. PARTICIPANTS: Poststroke patients (N=30) with subacute hemiparesis and severe deficits of the upper limb were enrolled. Fifteen patients were randomized to a standard rehabilitation program without orthosis and 15 patients received an experimental orthosis in addition to their standard rehabilitation program. INTERVENTION: The orthosis group wore the neutral functional realignment orthosis for at least 6 hours daily. MAIN OUTCOME MEASURES: Hand pain at rest (visual analog scale), wrist range of motion (Fugl-Meyer Assessment subscale), and edema of hand and wrist (circumferences). Outcome measures were assessed at time of randomization and after 13 weeks between groups. RESULTS: At baseline, 2 patients in each group complained about a painful hand. After 13 weeks, 8 subjects in the control group and 1 subject in the orthosis group complained of hand pain (P=.004). Mobility and edema evolved similarly in both groups. CONCLUSIONS: Neutral functional realignment orthoses have a preventive effect on poststroke hand pain, but not on mobility and edema in the subacute phase of recovery.