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Substantial evidence from previous clinical studies, randomized trials, and patient registries confirms the existence of significant differences in cardiac morphology, pathophysiology, prevalence of specific coronary artery disease (CAD), and clinical course of myocardial infarction (MI) between men and women. The aim of this review is to investigate the impact of sex or gender on the development and clinical course of MI, the mechanisms and features of left ventricular (LV) remodeling, and heart failure (HF). The main sex-related difference in post-MI LV remodeling is adverse LV dilatation in males versus concentric LV remodeling or concentric LV hypertrophy in females. In addition, women have a higher incidence of microvascular dysfunction, which manifests as impaired coronary flow reserve, distal embolism, and a higher prevalence of the no-reflow phenomenon. Consequently, impaired myocardial perfusion after MI is more common in women than in men. Regardless of age or other comorbidities, the incidence of reinfarction, hospitalization for HF, and mortality is significantly higher in females. There is therefore a "sex paradox": despite the lower prevalence of obstructive CAD and HF with reduced ejection fraction (HFrEF), women have a higher mortality rate after MI. Different characteristics of the coronary network, such as plaque formation, microvascular dysfunction, and endothelial inflammation, as well as the prolonged time to optimal coronary flow restoration, secondary mitral regurgitation, and pulmonary vascular dysfunction, lead to a worse outcome in females. A better understanding of the mechanisms responsible for MI occurrence, LV remodeling, and HF in men and women would contribute to optimized patient therapy that would benefit both sexes.