OBJECTIVE: To evaluate prognosis and recovery in patients with locked-in syndrome (LIS) receiving early intensive rehabilitative care. DESIGN: Consecutive sample and follow-up for 5 months to 6 years. SETTING: Three rehabilitation centers in Italy. PARTICIPANTS: Fourteen patients with LIS who underwent the same treatment and subsequently recovered. INTERVENTIONS: Intensive nursing care and intensive and early rehabilitative program, including physiotherapy and respiratory, swallowing, and speech training. For 4 patients, occupational therapy was performed; 4 subjects also had oculomotor training. After discharge, rehabilitative maintenance care continued for each patient. MAIN OUTCOME MEASURES: Motor recovery according to the Patterson and Grabois classification, functional improvement, and mortality rate. RESULTS: A significant motor recovery was found in 21% of subjects, within 3 to 6 months of onset of the morbid event; complete swallow recovery in 42%; verbal communication in 28%; communication through devices in 42%; effective bladder and bowel control in 35%; and good breathing patterns in 50%. At follow-up, the mortality rate was 14% and only 2 complications were reported. CONCLUSIONS: Intensive and early rehabilitation, begun within about 1 month of the morbid event, improved the functional recovery and reduced the mortality rate, which, as reported in the literature, had been 60% about 10 years ago. Further studies are necessary to confirm these data.