ABSTRACT: BACKGROUND:During hospitalization, older adults (+?65 years) are inactive, which puts them at risk of functional decline and loss of independence. Systematic strength training can prevent loss of functional performance and combining strength training with protein supplementation may enhance the response in muscle mass and strength. However, we lack knowledge about the effect of strength training commenced during hospitalization and continued after discharge in older medical patients. This assessor-blinded, randomized study investigated the effect of a simple, supervised strength training program for the lower extremities, combined with post-training protein supplementation during hospitalization and in the home setting for 4?weeks after discharge, on the effect on change in mobility in older medical patients. METHODS:Older medical patients (??65?years) admitted acutely from their home to the Emergency Department were randomized to either standard care or supervised progressive strength training and an oral protein supplement during hospitalization and at home 3?days/week for 4?weeks after discharge. The primary outcome was between-group difference in change in mobility from baseline to 4?weeks after discharge assessed by the De Morton Mobility Index, which assesses bed mobility, chair mobility, static and dynamic balance, and walking. Secondary outcomes were 24-h mobility, lower extremity strength, gait speed, grip strength and activities of daily living. RESULTS:Eighty-five patients were randomized to an intervention group (N?=?43) or a control group (N?=?42). In the intervention group, 43% were highly compliant with the intervention. Our intention-to-treat analysis revealed no between-group difference in mobility (mean difference in change from baseline to 4?weeks, -?4.17 (95% CI -?11.09; 2.74; p?=?0.24) nor in any of the secondary outcomes. The per-protocol analysis showed that the daily number of steps taken increased significantly more in the intervention group compared to the control group (mean difference in change from baseline to 4?weeks, 1033.4 steps (95% CI 4.1; 2062.7), p?=?0.049, adjusted for mobility at baseline and length of stay; 1032.8 steps (95% CI 3.6; 2061.9), p?=?0.049, adjusted for mobility at baseline, length of stay, and steps at baseline). CONCLUSIONS:Simple supervised strength training for the lower extremities, combined with protein supplementation initiated during hospitalization and continued at home for 4?weeks after discharge was not superior to usual care in the effect on change in mobility at 4?weeks in older medical patients. For the secondary outcome, daily number of steps, high compliance with the intervention resulted in a greater daily number of steps. Less than half of the patients were compliant with the intervention indicating that a simpler intervention might be needed. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01964482. Registered on 14 October 2013. Trial protocol PubMed ID (PMID), 27039381.