Background: This study was designed to assess whether measurement of the index of microvascular resistance (IMR) could help prospectively identify patients who develop periprocedural myocardial infarction (PPMI). Methods and results: IMR was measured in 54 patients before and following percutaneous coronary intervention (PCI) in a culprit vessel with a PressureWire using the equation IMR = PaHyp X TmnHyp (PdHyp-Pw/Pa Hyp-Pw). IMR was also measured in an angiographically normal reference vessel. The relative pre-IMR ratio (rPIMR) defined as IMR Culprit divided by IMR Non-Culprit was also calculated. Troponin was sequentially sampled up to 24 h following PCI. Mean troponin post-PCI was 0.37±0.8 ng/ml. 33 (61%) patients fulfilled the criteria for PPMI. IMR pre-PCI was the most significant correlate of post-PCI troponin (r=0.43 p=0.001), however, the number of balloon inflations (r=0.3, p=0.02) and rPIMR (r=0.33 p=0.017) were also correlated. IMR pre-PCI was higher in patients with periprocedural myocardial infarction compared with patients without PPMI (IMR pre-PCI 21.2±2.1 PPMI vs 15.6±1.8 No PPMI, p=0.02). The strongest predictor of troponin post-PCI was IMR pre-PCI (β 0.7, p=0.02). Both IMR pre- and rPIMR were predictive of PPMI (OR 11 (1.3 to 90.5) p=0.026, OR 1.09 (1 to 1.19) p=0.03, respectively). Conclusion: Microvascular function prior to PCI is an important determinant of PPMI. Measuring IMR pre-PCI and rPIMR may allow prospective identification of patients at risk of periprocedural myocardial infarction. Future studies in a larger cohort are required to establish the predictive ability of IMR in PPMI.