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Objective: To assess the effect of goal-directed mobilisation (GDM) on physical functioning in medical inpatients., Design: Randomised, controlled, single-centre, parallel, superiority trial with a 3-month follow-up and blinded outcome assessment., Setting: General internal medicine wards of a Swiss tertiary acute hospital, September 2021 to April 2023., Participants: Adults with expected hospitalisation of ≥5 days, physiotherapy prescription and ability to follow study procedures., Intervention: GDM during hospitalisation, which includes personal goal setting and a short session of patient education through a physiotherapist (experimental group), versus standard care (control group)., Outcome Measures: The primary outcome was the change in physical activity between baseline and day 5 (De Morton Mobility Index (DEMMI)). Secondary outcomes included in-hospital accelerometer-measured mobilisation time; in-hospital falls; delirium; length of stay; change in independence in activities of daily living, concerns of falling and quality of life; falls, readmission and mortality within 3 months., Results: The study was completed by 123 of 162 (76%) patients enrolled, with the primary outcome collected at day 5 in 126 (78%) participants. DEMMI Score improved by 8.2 (SD 15.1) points in the control group and 9.4 (SD 14.2) in the intervention group, with a mean difference of 0.3 (adjusted for the stratification factors age and initial DEMMI Score, 95% CI -4.1 to 4.8, p=0.88). We did not observe a statistically significant difference in effects of the interventions on any secondary outcome., Conclusions: The patient's physical functioning improved during hospitalisation, but the improvement was similar for GDM and standard of care. Improving physical activity during an acute medical hospitalisation remains challenging. Future interventions should target additional barriers that can be implemented without augmenting resources., Trial Registration Number: NCT04760392., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)