Objectives: Early detection of microvascular dysfunction after acute myocardial infarction (AMI) could identify patients at high risk of adverse clinical outcome, who may benefit from adjunctive treatment. Our objective was to compare invasively measured coronary flow reserve (CFR) and hyperaemic microvascular resistance (HMR) for their predictive power of long-term clinical outcome and cardiac magnetic resonance (CMR)-defined microvascular injury (MVI).Methods: Simultaneous intracoronary Doppler flow velocity and pressure measurements acquired immediately after revascularisation for AMI from five centres were pooled. Clinical follow-up was completed for 176 patients (mean age 60±10 years; 140(80%) male; ST-elevation myocardial infarction (STEMI) 130(74%) and non-ST-segment elevation myocardial infarction 46(26%)) with median follow-up time of 3.2 years. In 110 patients with STEMI, additional CMR was performed.Results: The composite end point of death and hospitalisation for heart failure occurred in 17 patients (10%). Optimal cut-off values to predict the composite end point were 1.5 for CFR and 3.0 mm Hg cm-1•sfor HMR. CFR <1.5 was predictive for the composite end point (HR 3.5;95% CI 1.1 to 10.8), but not for its individual components. HMR ≥3.0 mm Hg cm-1 s was predictive for the composite end point (HR 7.0;95% CI 1.5 to 33.7) as well as both individual components. HMR had significantly greater area under the receiver operating characteristic curve for MVI than CFR. HMR remained an independent predictor of adverse clinical outcome and MVI, whereas CFR did not.Conclusions: HMR measured immediately following percutaneous coronary intervention for AMI with a cut-off value of 3.0 mm Hg cm-1 s, identifies patients with MVI who are at high risk of adverse clinical outcome. For this purpose, HMR is superior to CFR.