Remote ischaemic conditioning (RIC) and postconditioning (PostC) are both potent activators of innate protection against ischaemia-reperfusion injury and have demonstrated cardioprotection in experimental and clinical ST-elevation myocardial infarction (STEMI) trials. However, their combined effects have not been studied in detail. The aim of this study was to evaluate if the co-application of intrahospital RIC and PostC has a more powerful effect on myocardial salvage compared with either PostC alone or control. This prospective, controlled, single-centre study randomized 696 STEMI patients to one of the following three groups: (i) combined intrahospital RIC + PostC in addition to primary percutaneous coronary intervention (PCI); (ii) PostC in addition to PCI; and (iii) conventional PCI (control). The primary endpoint myocardial salvage index was assessed by cardiac magnetic resonance (CMR) imaging within 3 days after infarction. Secondary endpoints included infarct size and microvascular obstruction (MVO) assessed by CMR. The combined clinical endpoint consisted of death, reinfarction, and new congestive heart failure within 6 months. The primary endpoint myocardial salvage index was significantly greater in the combined RIC + PostC group when compared with the control group (49 interquartile range 30-72 vs. 40 interquartile range 16-68, P = 0.02). Postconditioning alone failed to improve myocardial salvage when compared with conventional PCI (P = 0.39). The secondary endpoints, including infarct size and MVO, showed no significant differences between groups. Clinical follow-up at 6 months revealed no differences in the combined clinical endpoint between groups (P = 0.44). Combined intrahospital RIC + PostC in conjunction with PCI in STEMI significantly improves myocardial salvage in comparison with control and PostC. NCT02158468.