<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Aims</jats:title> <jats:p>This study sought to evaluate the association of coronary angiography-derived index of microcirculatory resistance (angio-IMR) measured after primary percutaneous coronary intervention (PPCI) with the evolution of infarct pathology during 3-month follow-up after ST-segment-elevation myocardial infarction (STEMI).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results</jats:title> <jats:p>Patients with STEMI undergoing PPCI were prospectively enrolled between October 2019 and August 2021. Angio-IMR was calculated using computational flow and pressure simulation immediately after PPCI. Cardiac magnetic resonance (CMR) imaging was performed at a median of 3.6 days and 3 months. A total of 286 STEMI patients (mean age 57.8 years, 84.3% men) with both angio-IMR and CMR at baseline were included. High angio-IMR (&gt;40 U) occurred in 84 patients (29.4%) patients. Patients with angio-IMR &gt;40 U had a higher prevalence and extent of MVO. An angio-IMR &gt;40 U was a multivariable predictor of infarct size with a three-fold higher risk of final infarct size &gt;25% (adjusted OR 3.00, 95% CI 1.23–7.32, P = 0.016). Post-procedure angio-IMR &gt;40 U significantly predicted presence (adjusted OR 5.52, 95% CI 1.65–18.51, P = 0.006) and extent (beta coefficient 0.27, 95% CI 0.01–0.53, P = 0.041) of myocardial iron at follow-up. Compared with patients with angio-IMR ≤40 U, those with angio-IMR &gt;40 U had less regression of infarct size and less resolution of myocardial iron at follow-up.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Angio-IMR immediately post-PPCI showed a significant association with the extent and evolution of infarct pathology. An angio-IMR &gt;40 U indicated extensive microvascular damage with less regression of infarct size and more persistent iron at follow-up.</jats:p> </jats:sec>