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To compare the effects of adding a progressive multimodal rehabilitation program to usual care (MRP + UC) versus UC alone on 1) functional mobility, strength, endurance and 2) ventilator weaning and discharge status of patients with ICU-acquired weakness (ICUAW) receiving prolonged mechanical ventilation (PMV).Randomized pilot trial of an individualized MRP + UC versus UC in middle-aged and older ICU survivors with ICUAW receiving PMV. Outcomes compare changes in strength, mobility, weaning success and discharge home from a long-term acute care hospital (LTACH) between the groups.Eighteen males and 14 females (age 60.3 ± 11.9 years) who received PMV for ≥14 days were enrolled. Despite no significant differences between groups in the changes in handgrip, gait speed, short physical performance battery or 6-min walk distance after treatment, the MRP + UC group had greater weaning success (87% vs. 41%, p < 0.01), and more patients discharged home than UC (53 vs. 12%, p = 0.05). Post hoc analyses, combining patients based on successful weaning or discharge home, demonstrated significant improvements in strength, ambulation and mobility.The addition of an MRP that improves strength, physical function and mobility to usual physical therapy in LTACH patients with ICUAW is associated with greater weaning success and discharge home than UC alone.A multimodal rehabilitation program for ICU survivors is feasible and well tolerated.Adding a multimodal rehabilitation program to usual care results in improved clinical outcomes.Improvements in mobility are associated with successful weaning and discharge home.