Acute medical units have increasingly been implemented in modern healthcare to ensure a fast track for treatment and care, thus increasing the number of patients being discharged. To avoid early readmissions, new approaches to discharging patients from these settings are needed. To investigate the clinical impact of a comprehensive nurse-led discharge intervention on patients being discharged home from an acute medical unit. The primary outcome was 30-days hospital readmission. Secondary outcomes were utilisation of healthcare, including contacting emergency departments, the general practitioner or after-hours physicians; patient experience; and health-related quality of life. This study was a non-blinded randomised clinical controlled trial with a 1 year enrolment period from November 2014 to 2015. Group assignment was performed by computer generated codes. The setting was a 34-bed acute medical unit at a Danish University Hospital. Non-surgical patients aged 18+ with more than one contact to hospitals during the last 12 months were eligible for inclusion. Furthermore, patients had to have been discharged home and had a follow-up appointment after discharge. The intervention consisted of (1) an assessment of the patient's overall situation, (2) an assessment of their comprehension of discharge recommendations, (3) a simple discharge letter targeting the individual patient's health literacy and (4) a follow-up telephone call 2 days post-discharge. The study was carried out by a research nurse and the 1st author. Data was collected from medical records, registers and questionnaires. Intention-to-treat and per protocol analysis were performed. In all, 200 participants were enrolled (101 intervention; 99 control). Of these, 17 were excluded due to transfer to another hospital department and 4 did not receive the full intervention, resulting in 86 in the intervention group and 93 in the control group. At 30 days post-discharge, 22/101 (22%) in the intervention group had at least one readmission vs. 19/99 (19%) in the control group. The total number of all-cause readmissions in the follow-up period was 0.28 (SD: 0.67) in the intervention group vs. 0.26 (SD: 0.63) in the control group. There were no statistically significant differences in baseline characteristics or any of the primary and secondary outcomes. A comprehensive nurse-led discharge model focusing on the individual patient's situation and needs was not capable of reducing readmissions and healthcare utilisation. No statistically significant effects on quality of life or patients' experiences of the discharge from the acute medical unit were observed. Copyright © 2019. Published by Elsevier Ltd.