Background Women are less likely to receive primary percutaneous coronary intervention (pPCI) than men. A potential reason is risk aversion because of the worse outcomes with pPCI among women. However, whether pPCI is associated with a comparable mortality benefit in men and women remains unknown. Methods and Results We selected patients admitted with a principal diagnosis of ST‐segment–elevation myocardial infarction in the National Inpatient Sample (2016–2018). We used propensity‐score matching to calculate average treatment effects of pPCI for in‐hospital mortality, major complications, length of stay, and cost. As a sensitivity analysis, we used logit models followed by a marginal command to calculate the average marginal effect. We included 413 500 weighted hospitalizations (30.7% women, 69.3% men). Women had more comorbidities except smoking and prior sternotomy. Compared with men, women were less likely to undergo angiography (81.0% versus 87.0%; adjusted odds ratio [OR], 0.77; 95% CI, 0.74–0.81; P <0.001) or pPCI (74.0% versus 82.0%; adjusted OR, 0.76; 95% CI, 0.73–0.79; P <0.001). There were no significant differences in average treatment effects of pPCI on mortality between men (−8.4% [−9.3% to −7.6%], P <0.001), and women (−9.5% [−10.8% to −8.3%], P <0.001) ( P interaction=0.16). This persisted in age‐stratified analyses (≥85, 65–84, 45–64, <45 years) and sensitivity analysis, excluding emergent admissions. The average treatment effects of pPCI on major complications were comparable except for acute stroke, leaving against medical advice, and palliative encounter. There were no differences in the average treatment effects of pPCI on length of stay, but the proportional increase in cost with pPCI was higher in women. Conclusions pPCI results in a comparable reduction in in‐hospital mortality in men and women. Nonetheless, risk‐adjusted rates of pPCI remain lower in women in contemporary US practice.