Background: Low muscle strength and muscle mass are associated with an increased length of hospital stay and higher mortality rate in inpatients. To what extent hospitalization affects muscle strength and muscle mass is unclear. Objective: We aimed to assess muscle strength and muscle mass at admission and during hospitalization in older patients and its relation with being at risk of geriatric conditions. Methods: The EMPOWER study included patients aged 70 years and older, admitted to 4 wards of the VU University Medical Center in the Netherlands between April and December 2015. At admission, patients were screened for being at risk of 4 geriatric conditions: delirium, falls, malnutrition, and functional disability. At admission and at discharge, muscle strength and muscle mass were assessed. Results: A total of 373 patients (mean age, standard deviation [SD]: 79.6, 6.38 years) were included at admission, and 224 patients (mean age, SD: 80.1, 6.32 years) at discharge. At admission, lower muscle strength in both female and male patients and low muscle mass in male patients were associated with being at risk of a higher cumulative number of geriatric conditions. Muscle strength increased during hospitalization, but no change in muscle mass was observed. Changes in muscle measures were not associated with being at risk of geriatric conditions. Discussion: Older patients with lower muscle strength and muscle mass at admission were at risk of a higher cumulative number of geriatric conditions. However, being at risk of geriatric conditions did not forecast further decrease in muscle strength and muscle mass during hospitalization.