Sex- and gender-associated differences determine the disease response to treatment. The study aimed to explore the hypothesis that progress in the management of STE-myocardial infarction (STEMI) overcomes the worse outcome in women. We performed an analysis of three randomized trials enrolling patients treated with primary PCI more than 10 years apart. PRAGUE-1,-2 validated the preference of transport for primary PCI over on-site fibrinolysis. PRAGUE-18 enrollment was ongoing at the time of the functional network of 24/7PCI centers, and the intervention was supported by intensive antiplatelets. The proportion of patients with an initial Killip ≥ 3 was substantially higher in the more recent study (0.6 vs. 6.7%, = 0.004). Median time from symptom onset to the door of the PCI center shortened from 3.8 to 3.0 h, < 0.001. The proportion of women having total ischemic time ≤3 h was higher in the PRAGUE-18 (OR 95% C.I. 2.65 2.03-3.47). However, the percentage of patients with time-to-reperfusion >6 h was still significant (22.3 vs. 27.2% in PRAGUE-18). There was an increase in probability for an initial TIMI flow >0 in the later study (1.49 1.0-2.23), and also for an optimal procedural result (4.24 2.12-8.49, < 0.001). The risk of 30-day mortality decreased by 61% (0.39 0.17-0.91, = 0.029). The prognosis of women with MI treated with primary PCI improved substantially with 24/7 regional availability of mechanical reperfusion, performance-enhancing technical progress, and intensive adjuvant antithrombotic therapy. A major modifiable hindrance to achieving this benefit in a broad population of women is the timely diagnosis by health professional services.