Background: Sex-based differences in the clinical presentation and outcomes are well-established in patients hospitalized for geriatric syndromes. We aimed to investigate sex differences in response to in-hospital exercise on function, strength, cognition, and quality of life in acute care admissions.

Methods: 570 patients (mean age 87 years, 298 females [52.3%]) admitted to acute care for elderly units were randomized to multicomponent exercise emphasizing progressive resistance training or usual care. Functional assessments included Short Physical Performance Battery (SPPB), grip strength, Mini-Mental State Examination (MMSE), and health-related quality of life (EQ-VAS).

Results: Exercising females showed more significant SPPB improvements than males (between-group difference 1.48 points, p = 0.027), exceeding the minimal clinically significant difference. While female participants significantly increased handgrip strength and male patients improved cognition after in-hospital exercise compared to the control group (all p < 0.001), no sex differences occurred.

Conclusions: Females demonstrate more excellent physical function improvements compared to male older patients. Findings highlight the importance of tailored exercise incorporating patient factors like biological sex in geriatric medicine.

Trial registration: NCT04600453.