This study sought to investigate the relationship between the index of microcirculatory resistance (IMR) and periprocedural myocardial necrosis in patients with unstable angina pectoris (UAP). Fifty-seven UAP patients undergoing elective percutaneous coronary intervention (PCI) of a single lesion were recruited. A pressure-temperature sensor wire was used to measure IMR immediately after PCI. Total creatine kinase-MB (CK-MB) and troponin I (TNI) were measured every 8 h after PCI until they began to decline. Of the 57 patients studied, 22 had periprocedural myocardial infarction (MI) according to TNI. Post-PCI IMR >31 U had 86% sensitivity and 91% specificity for predicting periprocedural MI. There are a strong positive correlation between IMR and peak TNI (r = 0.805, p = 0.001), and a moderate positive correlation between IMR and peak CK-MB (r = 0.608, p = 0.003). Periprocedural myocardial injury, even in small area, during reperfusion is associated with impaired microcirculatory integrity as evaluated by IMR. Post-PCI IMR is independent predictive of developing periprocedural MI in patients with UAP, and, therefore, potentially enables a triage of higher risk patients to more intensive therapy.