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Coronary flow reserve (CFR) assessment by transthoracic ultrasound of the left anterior descending (LAD) artery during dipyridamole stress echocardiography has been shown to predict prognosis in large unselected populations. Low values of CFR are strongly correlated with significant stenosis of the LAD; aim of the present study was to assess the prognostic impact of CFR in patients recovering from an acute coronary syndrome (ACS) with proven absence of LAD disease.From an overall cohort of 325 patients with ACS who underwent a high-dose dipyridamole stress with combined assessment of CFR in the LAD and wall motion, 152 patients without LAD disease (stenosis <50%) were included in the present analysis; all subjects underwent coronary angiography and were subsequently monitored for the incidence of major cardiac events (MACE).After a median follow-up of 29 months, 22 patients developed MACE. Patients who experienced MACE differed from stable patients in terms of age, prevalence of diabetes, and CFR. Receiver-operating characteristic curve analysis defined a CFR <2.25 as the optimal cut point for prediction of MACE. Cox multivariable analysis for the prediction of MACE demonstrated independent predictive value only for CFR <2.25, smoking status, and number of stenotic vessels at angiogram.In high-risk patients with ACS, even in the absence of LAD disease, CFR significantly improves prediction of adverse events when added to standard evaluation. This finding supports a role of CFR in the risk stratification early after ACS and is in context with the concept that CFR reflects global atherosclerotic burden, endothelial dysfunction, and microvascular damage, more than just mirroring focal LAD disease.