Purpose <p>The impact of myocardial scar on coronary microcirculation is not well understood. This study aims to evaluate the association between microvascular resistance reserve (MRR) and scar tissue.</p> Methods <p>In this post-hoc analysis of the PACIFIC 2 trial, symptomatic patients with prior myocardial infarction (MI) and/or percutaneous coronary intervention (PCI) underwent [¹⁵O]H₂O positron emission tomography (PET), cardiac magnetic resonance (CMR) imaging, and fractional flow reserve (FFR). MRR was assessed utilizing PET-derived coronary flow reserve and FFR measurements. Scar quantification was assessed by CMR late gadolinium enhancement (LGE). Vessel LGE burden was defined as the scar tissue proportion in each myocardial territory. Total LGE burden was defined as the proportion of overall scar.</p> Results <p>The study included 154 patients with 397 vessels with a mean MRR of 3.56 ± 1.24. Patients with any scar tissues (LGE &gt; 0%) exhibited a lower MRR in every myocardial territory than those without scar tissues. After adjusting for cardiovascular risk factors, either vessel LGE burden (β =-0.013, <i>P</i> = 0.006) or total LGE burden (β =-0.039, <i>P</i> = 0.002) independently predicted a reduced MRR. Compared to myocardial territories without scar tissues (LGE burdens = 0%), MRR was significantly lower in myocardial territories with vessel LGE burden = 0% + total LGE burden &gt; 0%, and in myocardial territories with both LGE burdens &gt; 0%.</p> Conclusion <p>Scar burden was negatively associated with MRR in patients with prior MI and/or PCI. Our findings indicate that both the proportion of myocardial scar in the vascular territory and the overall myocardial scar affect the microcirculation of individual vascular territories.</p> Clinical trial number <p>Not applicable.</p>