BACKGROUND: Protein supplementation and mobility-based rehabilitation programs (MRP) individually improve functional outcomes in survivors of critical illness. We hypothesized that combining MRP therapy with high protein supplementation is associated with greater weaning success from prolonged mechanical ventilation (PMV) and increased discharge home in this population. METHODS: We conducted a retrospective analysis assessing the effects of an MRP on a cohort of survivors of critical illness. All received usual care (UC) rehabilitation. The MRP group received 3 additional MRP sessions each week for a maximum of 8 weeks. Subjects were prescribed nutrition and classified as receiving high protein (HPRO) or low protein (LPRO), based on a recommended 1.0 g/kg/d, and then the subjects were categorized into 4 groups: MRP+HPRO, MRP+LPRO, UC+HPRO, and UC+LPRO. RESULTS: A total of 32 subjects were enrolled. The MRP+HPRO group had greater weaning success (90% vs 38%, P 5 .045) and a higher rate of discharge home (70% vs 13%, P 5 .037) compared to UC+LPRO group. The MRP+HPRO group had a higher, nonsignificant rate of discharge home compared to the MRP+LPRO (70% vs 20%, P 5 .10). CONCLUSIONS: Combining high protein with mobility-based rehabilitation was associated with increased rates of discharge home and ventilator weaning success in survivors of critical illness. Further studies are needed to evaluate the role of combined exercise and nutrition interventions in this population.