Background: We hypothesized that female sex is a treatment effect modifier of blood flow and related 30-day mortality after primary percutaneous coronary intervention (PCI) for ST-segment–elevation myocardial infarction and that the magnitude of the effect on outcomes differs depending on delay to hospital presentation. ----- Methods and Results: We identified 2596 patients enrolled in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry from 2010 to 2016. Primary outcome was the occurrence of 30-day mortality. Key secondary outcome was the rate of suboptimal post-PCI Thrombolysis in Myocardial Infarction (TIMI; flow grade 0–2). Multivariate logistic regression and inverse probability of treatment weighted models were adjusted for baseline clinical covariates. We characterized patient outcomes associated with a delay from symptom onset to hospital presentation of ≤120 minutes. In multivariable regression models, female sex was associated with postprocedural TIMI flow grade 0 to 2 (odds ratio [OR], 1.68; 95% CI, 1.15– 2.44) and higher mortality (OR, 1.72; 95% CI, 1.02–2.90). Using inverse probability of treatment weighting, 30-day mortality was higher in women compared with men (4.8% versus 2.5%; OR, 2.00; 95% CI, 1.27–3.15). Likewise, we found a significant sex difference in post-PCI TIMI flow grade 0 to 2 (8.8% versus 5.0%; OR, 1.83; 95% CI, 1.31–2.56). The sex gap in mortality was no longer significant for patients having hospital presentation of ≤120 minutes (OR, 1.28; 95% CI, 0.35–4.69). Sex difference in post- PCI TIMI flow grade was consistent regardless of time to hospital presentation. ----- Conclusions: Delay to hospital presentation and suboptimal post-PCI TIMI flow grade are variables independently associated with excess mortality in women, suggesting complementary mechanisms of reduced survival.