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To evaluate the prevalence and magnitude of weakness in patients receiving chronic mechanical ventilation and the impact of providing aggressive whole-body rehabilitation on conventional weaning variables, muscle strength, and overall functional status.Retrospective analysis of 49 consecutive patients.Multidisciplinary ventilatory rehabilitation unit in an academic medical center.Forty-nine consecutive chronic ventilator-dependent patients referred to a tertiary care hospital ventilator rehabilitation unit.None.Patients were 58 ± 7 yrs old with multiple etiologies for respiratory failure. On admission, all patients were bedridden and had severe weakness of upper and lower extremities measured by a 5-point muscle strength score and a 7-point Functional Independence Measurement. Postrehabilitation, patients had increases in upper and lower extremity strength (p < .05) and were able to stand and ambulate. All weaned from mechanical ventilation, but three required subsequent intermittent support. Six patients died before hospital discharge. Upper extremity strength on admission inversely correlated with time to wean from mechanical ventilation (R = .72, p < .001).Patients receiving chronic ventilation are weak and deconditioned but respond to aggressive whole-body and respiratory muscle training with an improvement in strength, weaning outcome, and functional status. Whole-body rehabilitation should be considered a significant component of their therapy.