Background Recent data from the National Cardiovascular Data Registry indicate that women with ST-segment-elevation myocardial infarction (STEMI) continue to have higher mortality and reported delays in treatment compared with men. We aimed to determine whether the sex difference in mortality exists when treatment disparities are reduced. Methods Using a prospective regional percutaneous coronary intervention (PCI)–based STEMI system database with a standardized STEMI protocol, we evaluated baseline characteristics, treatment, and clinical outcomes of STEMI patients stratified by sex. Results From March 2003 to January 2016, 4,918 consecutive STEMI patients presented to the Minneapolis Heart Institute at Abbott Northwestern Hospital regional STEMI system including 1,416 (28.8%) women. Compared with men, women were older (68.4 vs 60.9 years) with higher rates of hypertension (66.7% vs 55.7%), diabetes (21.7% vs 17.4%), and cardiogenic shock (11.5% vs 8.0%) (all P < .001). Pre-revascularization medications and PCI were performed with same frequencies, but women were less likely to receive statin or antiplatelet therapy at discharge. After age adjustment, women had similar in-hospital mortality to men (5.1% vs 4.8%, P = .60) despite slightly longer door-to-balloon time (95 vs 92 minutes, P = .004). Five-year follow-up confirmed absence of a sex disparity in age-adjusted survival post-STEMI. Conclusions Previously reported treatment disparities between men and women are diminished in a regional PCI-based STEMI system using a standardized STEMI protocol. No sex differences in short-term or long-term age-adjusted mortality are present in this registry despite some treatment disparities. These results suggest that STEMI health care disparities and mortality in women can be improved using STEMI protocols and systems.