Ischemic heart disease (IHD) is the leading cause of mortality worldwide, accounting for over 7 million deaths per year. ST-elevation myocardial infarction (STEMI) accounts for nearly one third of acute coronary syndromes. Despite improved STEMI patient care achieved mainly by timely primary percutaneous coronary intervention (PCI) mortality remains unacceptably high, ranging between 6 and 14%. High mortality rates may partly be ascribed to ischemia-reperfusion injury (IRI) which is believed to account for up to 40-50% of infarct size. Several pharmacological alternatives have been attempted to prevent IRI in promising animal experiments nevertheless clinical translation has been disappointing. On the opposite side, ischemic conditioning (IC) by short cycles of ischemia-reperfusion applied before, during or after a major ischemic event has clearly been shown to attenuate IRI in various clinical scenarios. Moreover, even repeated bouts of limb ischemia are cardioprotective, so-called remote IC (RIC). In 2010, Bøtker et al. showed improved myocardial salvage index as assessed by single photon emission computed tomography 30 days after PCI in patients randomly assigned to receive concomitant RIC whereas Rentoukas et al. found higher proportions of ST-segment resolution with adjunctive RIC compared with PCI alone, although significant reductions in troponin I peaks only reached statistical significance in a subgroup undergoing both RIC and morphine therapy combined with PCI. More recently, the group of Bøtker evaluated the long-term effect of RIC on the very same population they initially recruited (166 patients underwent PCI with adjunctive RIC and 167 patients simply underwent PCI) and showed improved long-term prognosis for patients that underwent adjunctive RIC as regards the composite endpoint of adverse cardiac and cerebrovascular events: all-cause mortality, MI, readmission for heart failure (HF), and ischaemic stroke/transient ischaemic attack. However, although very promising, their results are inconclusive as regards cardiovascular mortality and HF development, since the study was not powered to show differences in these clinical events. Large scale studies addressing major adverse cardiovascular events are warranted.