The role of heart rate (HR) reserve (HRR) in the risk stratification of patients who undergo dobutamine stress echocardiography is not well defined. This study evaluated 1,323 patients (mean age 63 +/- 13 years, 47% men) who underwent dobutamine stress echocardiography. Abnormal stress echocardiographic results were defined as those with stress-induced ischemia. HRR was defined as [(peak HR - HR at rest)/(220 - age - HR at rest)] x 100, with HRR <70% defined as low. Follow-up data (2.7 +/- 1.1 years) for confirmed myocardial infarction (n = 16) and cardiac death (n = 58) were obtained. HRR risk stratified patients into normal and abnormal subgroups (event rate 1.1%/year vs 4.2%/year, p <0.0001) and further risk stratified patients into normal (adjusted HR 1 [reference] vs 2.88, p = 0.04) and abnormal (adjusted HR 4.17 vs 10.09, p <0.0001) stress echocardiography groups. Low HRR (relative risk [RR] 2.15, 95% confidence interval [CI] 1.23 to 4.01, p = 0.013) was an independent predictor of cardiac event even after controlling for standard cardiovascular risk factors, other stress electrocardiographic variables, and stress echocardiographic variables. Low HRR (chi-square 32) was superior to 85% maximum predicted HR (MPHR; chi-square 18) and provided incremental value over stress echocardiography and 85% MPHR (global chi-square increased from 48.3 to 54 to 61.3, p <0.0001) in a model consisting of stress echocardiography, MPHR, and HRR. In conclusion, HRR can further risk stratify patients who undergo dobutamine stress echocardiography and provides independent and incremental prognostic value over standard cardiovascular risk factors and also independent of echocardiographic myocardial ischemia and left ventricular dysfunction and is superior to 85% MPHR. In the setting of low HRR, normal stress echocardiographic results are prognostically less benign, whereas abnormal stress echocardiographic results are prognostically more malignant.