The additive prognostic value of coronary flow reserve (CFR) over regional wall motion has been established, but there is more than a binary (normal–abnormal) response in CFR, which can be continuously titrated. We assessed the prognostic value of quartiles of CFR, evaluated by transthoracic Doppler of the left anterior descending coronary artery (LAD), in patients with known or suspected coronary artery disease (CAD). One thousand six hundred twenty patients (1,006 men, 64 ± 11 years of age) underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echocardiography with CFR evaluation of LAD by Doppler and coronary angiography. Patients were followed up for a median of 19 months. Mean CFR in the entire population was 2.25 ± 0.65. Stress echocardiogram was positive for ischemia in 480 patients (30%). Obstructive (≥70% vessel stenosis) CAD at angiography was present in 650 patients (40%). During follow-up, there were 298 events (42 deaths, 73 ST-elevation myocardial infarctions, and 183 non–ST-elevation myocardial infarctions). Patients (n = 399) undergoing revascularization were censored. With the Kaplan-Meier method, the first quartile of CFR (≤1.80) was associated with a worse (p <0.0001) event rate than other quartiles in the entire population and in patients with no ischemia at stress echocardiography. Furthermore, the second quartile of CFR (1.81 to 2.16) was predictive of increased (p <0.0001) risk compared to the higher quartiles. In conclusion, Doppler echocardiographically derived CFR in LAD is a strong and independent prognostic predictor in patients with known or suspected CAD, but the spectrum of prognostic stratifications is expanded if the response is titrated according to a continuous scale rather than artificially dichotomized.