Primary percutaneous coronary intervention (PCI) decreases myocardial damage in patients with ST-elevation myocardial infarction (STEMI). Cellular reperfusion injury associated with calcium overload may limit myocardial salvage. We previously showed (CASTEMI trial) that caldaret (MCC-135), which modulates myocardial calcium handling when administered before PCI in patients with STEMI, did not change residual left ventricular (LV) function. The aim of this subanalysis was to examine whether caldaret decreases the incidence of LV dysfunction (LV ejection fraction <or=30%) in patients with STEMI undergoing primary PCI. Of 387 patients enrolled in the CASTEMI study, 239 had single-photon emission computed tomographic data on days 7 and 30 after the infarct. The incidence of LV dysfunction in patients receiving low- and high-dose caldaret was compared with placebo. At day 30 after the infarct, there was a significant decrease in the incidence of LV dysfunction in patients receiving low and high doses of caldaret versus placebo (8.0%, 6.9% vs 17.5%, p <0.05 for the 2 comparisons). This difference was more pronounced in patients with anterior wall MI and Thrombolysis In Myocardial Infarction grade 0/1 flow. In this group, 52% decrease in the incidence of LV dysfunction was observed already on day 7 after the infarct (p = 0.026). The incidence of an LV ejection fraction <or=30% was significantly decreased between day 7 and day 30 in patients treated with the 2 doses of caldaret and was unchanged in the placebo group. In conclusion, treatment with intravenous caldaret in patients with STEMI undergoing primary PCI is associated with a significant decrease in the incidence of severe LV dysfunction.