The POST (the effects of postconditioning on myocardial reperfusion in patients with ST-Segment elevation myocardial infarction) study showed that ischemic postconditioning did not improve myocardial reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). However, it has not been determined whether postconditioning is effective in women. This study sought to evaluate the impact of sex differences on ischemic postconditioning during the primary PCI. We analyzed clinical outcomes at 1 year in the 537 men and 163 women with STEMI, who were randomized to the postconditioning or to the conventional PCI group. Women were older, had higher rates of hypertension, were less likely to be current smokers, and had longer symptom-to-reperfusion time. The rate of major adverse cardiac events (MACE: a composite of death, myocardial infarction, severe heart failure, stent thrombosis, or target vessel revascularization) at 1 year was higher in women compared to men (9.8% vs. 5.4%, p = 0.044). MACE was significantly higher in women compared to men in the postconditioning group (12.2% vs. 5.4%, p = 0.042), but not in the conventional PCI group (7.9% vs. 5.4%, p = 0.391). However, women was not an independent predictor after adjusting baseline risk factors, angiographic and procedural parameters (HR 2.67, 95% CI 0.68–10.5, p = 0.158). Despite women having more adverse clinical characteristics, their prognosis was similar to men in the conventional group. Although women showed a higher rate of the MACE compared to men, women were not an independent predictor in the postconditioning group.