BACKGROUND & AIM: Stress metabolism is associated with accelerated loss of muscle that has large consequences for the old medical patient. The aim of this study was to investigate if an intervention combining protein and resistance training was more effective in counteracting loss of muscle than standard care. Secondary outcomes were changes in muscle strength, functional ability and body weight. METHODS: 29 acutely admitted old (>65 years) patients were randomly assigned to the intervention (n = 14) or to standard care (n = 15). The Intervention Group received 1.7 g protein/kg/day during admission and a daily protein supplement (18.8 g protein) and resistance training 3 times per week the 12 weeks following discharge. Muscle mass was assessed by Dual-energy X-ray Absorptiometry. Muscle strength was assessed by Hand Grip Strength and Chair Stand Test. Functional ability was assessed by the de Morton Mobility Index, the Functional Recovery Score and the New Mobility Score. Changes in outcomes from time of admission to three-months after discharge were analysed by linear regression analysis. RESULTS: The intention-to-treat analysis showed no significant effect of the intervention on lean mass (unadjusted: β-coefficient = -1.28 P = 0.32, adjusted for gender: β-coefficient = -0.02 P = 0.99, adjusted for baseline lean mass: β-coefficient = -0.31 P = 0.80). The de Morton Mobility Index significantly increased in the Control Group (β-coefficient = -11.43 CI: 0.72-22.13, P = 0.04). No other differences were found. CONCLUSION: No significant effect on muscle mass was observed in this group of acutely ill old medical patients. High compliance was achieved with the dietary intervention, but resistance training was challenging. Clinical trials identifier NCT02077491.