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31 p.-5 fig.-4 tab.-6 fig. supl.-1 tab. supl., Background-Microcirculation is a decisive factor in tissue reperfusion inadequacy following myocardial infarction (MI).Nonetheless, experimental assessment of blood flow in microcirculation remains a bottleneck. We sought to model blood flow properties in coronary microcirculation at different time points after MI and to compare them with healthy conditions to obtain insights into alterations in cardiac tissue perfusion., Methods and Results-We developed an image-based modeling framework that permitted feeding a continuum flow model with anatomical data previously obtained from the pig coronary microvasculature to calculate physiologically meaningful permeability tensors. The tensors encompassed the microvascular conductivity and were also used to estimate the arteriole–venule drop in pressure and myocardial blood flow. Our results indicate that the tensors increased in a bimodal pattern at infarcted areas on days 1 and 7 after MI while a nonphysiological decrease in arteriole–venule drop in pressure was observed; contrary, the tensors and the arteriole–venule drop in pressure on day 3 after MI, and in remote areas, were closer to values for healthy tissue. Myocardial blood flow calculated using the condition-dependent arteriole–venule drop in pressure decreased in infarcted areas. Last, we simulated specific modes of vascular remodeling, such as vasodilation, vasoconstriction, or pruning, and quantified their distinct impact on microvascular conductivity., Conclusions-Our study unravels time- and region-dependent alterations of tissue perfusion related to the structural changes occurring in the coronary microvasculature due to MI. It also paves the way for conducting simulations in new therapeutic interventions in MI and for image-based microvascular modeling by applying continuum flow models in other biomedical scenarios., The research leading to these results has received funding from the People Programme (Marie Curie Action) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant Agreement 608027 and from the Spanish Ministerio de Ciencia, Innovación y Universidades (SAF2017-83229-R) to Arroyo. The CNIC (Centro Nacional de Investigaciones Cardiovasculares) is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Popel was supported by NIH grant R01HL101200 from the National Heart, Lung and Blood Institute, NHLBI. Santos acknowledges founding from Ministerio de Ciencia, Innovación y Universidades (TEC2015-66978-R). El-Bouri was funded by a Doctoral Training Partnership studentship, grant reference EP/M50659X/1.