After recovery from critical illness, many patients commonly experience debilitating muscle wasting and weakness, which adversely impacts their functional recovery. These consequences are particularly common in patients who required prolonged mechanical ventilation -- a subgroup of chronically critically ill patients for whom recovery is especially challenging. Current rehabilitation strategies, including standard physical therapy, are insufficient to restore most ventilated patients to their previous level of functional independence. As such, many of these patients require long-term placement in nursing homes. Neuromuscular electrical stimulation (NMES) is an innovative technique that augments muscle size, strength and exercise capacity in deconditioned patients with chronic diseases. NMES is well-tolerated without adverse effects. Because it requires minimal cooperation and does not burden the cardiopulmonary system, NMES may be ideal for reconditioning the muscles and facilitating the return of functional independence in patients requiring prolonged ventilation. Thus, the primary goal of this proposal is to test the effectiveness of NMES (in combination with a standardized physical therapy program) in facilitating independent functional activities in patients requiring prolonged ventilation. To minimize confounders related to acute critical illness patient will be recruited following transfer to a long-term acute care hospital (LTACH) for extended rehabilitation and weaning. Patients will be randomly assigned to receive NMES or sham- NMES of the quadriceps, tibialis anterior, and gastrocnemius muscles of both legs. Both NMES and sham- NMES groups will receive a standardized physical therapy program. Independence in performing functional activities during the LTACH stay (primary outcome) will be quantified using the Functional Status Score for the Intensive Care Unit (FSS-ICU). The long-term impact of NMES on patient-reported outcomes (Barthel index, SF-36, pulmonary functional status scale [PFSS]) and performance-based measurement (Timed-up and go [TUG] test) will also be assessed at three and six months after discharge from the LTACH. Mechanisms of action of NMES in ventilated patients are largely unknown. Accordingly, physiologic response to NMES will be investigated by measuring muscle size (using ultrasonography) and muscle function (using hand-held dynamometry). Information gained from this study about the efficacy of NMES (in combination with a standardized physical therapy program) could provide a paradigm shift in strategies employed at facilitating functional independence in patients requiring prolonged mechanical ventilation. 1