The remote ischemic PReconditioning In Non-Cardiac surgEry (PRINCE) trial was a multinational, double-blind trial in which 1213 patients undergoing noncardiac surgical procedures were randomly assigned to receive remote ischaemic preconditioning (RIPC) or sham-RIPC after general anaesthesia and before surgery to reduce myocardial injury. Postoperative myocardial injury, defined alone by postoperative high-sensitivity troponin above the highest 99th percentile of reference values, occurred in 215/566 patients (38.0%) in the RIPC group and in 223/596 patients (37.4%) in the sham-RIPC group. The PRINCE trial adds to an apparently contradictory literature on the role of RIPC in perioperative medicine. We discuss both trial-specific and mechanistic reasons to explain these discrepancies, and we contend that a role for RIPC in minimising organ injury as a result of noncardiac surgery remains possible.