•The results of this study suggest that oral nutritional supplements administered in the Medication Pass Nutritional Supplement Program (MEDPass) mode do not negatively affect appetite.•According to the oral nutritional supplements administration mode, there was no difference in energy and protein coverage between patients with weak or normal handgrip strength.•Patients with weak handgrip strength and MEDPass administration tended to have the lowest energy and protein coverage.•In clinical practice, appetite and satiety in patients with weak handgrip strength should be monitored, and the oral nutritional supplements administration mode should be adapted accordingly. It is important to individualize nutrition therapy and to identify whether certain patient groups benefit from a specific intervention such as oral nutritional supplements (ONS). This study investigated whether patients with weak handgrip strength (HGS) benefit better from ONS administration in the Medication Pass Nutritional Supplement Program (MEDPass) mode regarding the individual coverage of energy and protein requirements throughout their hospitalization. A secondary analysis of the intention-to-treat data set of the randomized controlled MEDPass trial was conducted. Weak HGS was defined as <27 kg for men and <16 kg for women. Linear mixed-effect models adjusted for the stratification factors energy density of ONS and nutritional risk screening 2002 score were used to address the aim of the study. We included 188 participants. Energy and protein coverage did not differ between the patients with weak or normal HGS depending on ONS administration mode (P = 0.084, P = 0.108). Patients with weak HGS and MEDPass administration mode tended to have the lowest energy and protein coverage (estimated mean, 77.2%; 95% confidence interval CI, 69.3%–85% and estimated mean, 95.1%; 95% CI, 85.3%–105%, respectively). Patients with weak HGS and conventional ONS administration had the highest energy and protein coverage (estimated mean, 90%; 95% CI, 82.8%–97.2% and estimated mean, 110.2%; 95% CI, 101.3%–119%, respectively). No clear recommendations regarding the mode of ONS administration depending on HGS can be made. In clinical practice, appetite and satiety in patients with weak HGS should be monitored, and the ONS administration mode should be adjusted accordingly.