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Yes / Introduction Heart failure affects 26 million people globally, approximately 900 thousand people in the UK, and is increasing in incidence. Appropriate management of medicines for heart failure at the time of hospital discharge reduces readmissions, improves quality of life and increases survival. The Improving the Safety and Continuity Of Medicines management at Transitions (ISCOMAT) trial tests the effectiveness of the Medicines at Transition Intervention (MaTI), which aims to enhance self-care and increase community pharmacy involvement in the medicines management of heart failure patients. Methods and analysis ISCOMAT is a parallel-group cluster randomised controlled trial, randomising 42 National Health Service trusts with cardiology wards in England on a 1:1 basis to implement the MaTI or treatment as usual. Around 2100 patients over the age of 18 admitted to hospital with heart failure with at least moderate left ventricular systolic dysfunction within the last 5 years, and planned discharge to the geographical area of the cluster will be recruited. The MaTI consists of training for staff, a toolkit for participants, transfer of discharge information to community pharmacies and a medicines reconciliation/review. Treatment as usual is determined by local policy and practices. The primary outcome is a composite of all-cause mortality and heart failure-related hospitalisation at 12 months postregistration obtained from national electronic health records. The key secondary outcome is continued prescription of guideline-indicated therapies at 12 months measured via patient-reported data and Hospital Episode Statistics. The trial contains a parallel mixed-methods process evaluation and an embedded health economics study. / The study was funded as part of a National Institute for Health Research Programme Grant for Applied Research (RP-PG-0514-20009).