Background-Microvascular function is increasingly being recognized as an important marker of risk in coronary artery disease, and may be accurately assessed by intracoronary Doppler flow velocity measurements. In the setting of STsegment-elevation myocardial infarction there are limited data regarding the prognostic value of microvascular function in both infarct-related and reference coronary arteries for long-term clinical outcome. We sought to determine the prognostic value of microvascular function, as assessed by Doppler flow velocity measurements, for cardiac mortality after primary percutaneous coronary intervention for acute ST-segment-elevation myocardial infarction. Methods and Results-Between April 1997 and August 2000, we included 100 consecutive patients with a first anterior wall ST-segment-elevation myocardial infarction. Immediately after primary percutaneous coronary intervention, intracoronary Doppler flow velocity was measured in the infarct-related artery, to determine coronary flow velocity reserve (CFVR), diastolic deceleration time, and the presence of systolic retrograde flow, as well as in a reference vessel to determine reference vessel CFVR. The primary end point was cardiac mortality at 10-year follow-up. Complete follow-up was obtained in 94 patients (94%). At 10-year follow-up, cardiac mortality amounted to 14%. Cardiac mortality amounted to 5% when reference vessel CFVR was normal (≥2.1), in contrast to 31% when abnormal (<2.1; P=0.001). Reference vessel CFVR <2.1 was associated with a 4.09 increase in long-term cardiac mortality hazard after multivariate adjustment for identified predictors for cardiac mortality (hazard ratio, 4.09; 95% confidence interval, 1.18-14.17; P=0.03) Conclusions-Microvascular dysfunction, measured by reference vessel CFVR determined after primary percutaneous coronary intervention for acute anterior wall ST-segment-elevation myocardial infarction is associated with a significantly increased long-term cardiac mortality. (Circ Cardiovasc Interv. 2013;6:207-215.)