BACKGROUND: Novel cardioprotective strategies are required to improve clinical outcomes in high risk patients undergoing coronary artery bypass graft (CABG) ± valve surgery. Remote ischemic preconditioning (RIC), in which brief episodes of non-lethal ischemia and reperfusion are applied to the arm or leg, has been demonstrated to reduce perioperative myocardial injury following CABG ± valve surgery. Whether RIC can improve clinical outcomes in this setting is unknown and is investigated in the effect of remote ischemic preconditioning on clinical outcomes (ERICCA) trial in patients undergoing CABG surgery. (ClinicalTrials.gov Identifier: NCT01247545). METHODS: The ERICCA trial is a multicentre randomized double-blinded controlled clinical trial which will recruit 1,610 high-risk patients (Additive Euroscore ≥ 5) undergoing CABG ± valve surgery using blood cardioplegia via 27 tertiary centres over 2 years. The primary combined endpoint will be cardiovascular death, non-fatal myocardial infarction, coronary revascularization and stroke at 1 year. Secondary endpoints will include peri-operative myocardial and acute kidney injury, intensive care unit and hospital stay, inotrope score, left ventricular ejection fraction, changes of quality of life and exercise tolerance. Patients will be randomized to receive after induction of anesthesia either RIC (4 cycles of 5 min inflation to 200 mmHg and 5 min deflation of a blood pressure cuff placed on the upper arm) or sham RIC (4 cycles of simulated inflations and deflations of the blood pressure cuff). IMPLICATIONS: The findings from the ERICCA trial have the potential to demonstrate that RIC, a simple, non-invasive and virtually cost-free intervention, can improve clinical outcomes in higher-risk patients undergoing CABG ± valve surgery.