CONTEXT:Chronotropic incompetence, an attenuated heart rate response to exercise, is a predictor of all-cause mortality in healthy populations. This association may be independent of exercise-induced myocardial perfusion defects. OBJECTIVE:To examine the prognostic significance of chronotropic incompetence in a low-risk cohort of patients referred for treadmill stress testing with thallium imaging. DESIGN:Prospective cohort study conducted between September 1990 and December 1993. SETTING:Tertiary care academic medical center. PATIENTS:Consecutive patients (1877 men and 1076 women; mean age, 58 years) who were not taking beta-blockers and who were referred for symptom-limited treadmill thallium testing. MAIN OUTCOME MEASURES:Association of chronotropic incompetence, defined as either failure to achieve 85% of the age-predicted maximum heart rate or a low chronotropic index, a heart rate response measure that accounts for effects of age, resting heart rate, and physical fitness, with all-cause mortality during 2 years of follow-up. RESULTS:Three hundred sixteen patients (11%) failed to reach 85% of the age-adjusted maximum heart rate, 762 (26%) had a low chronotropic index, and 612 (21%) had thallium perfusion defects. Ninety-one patients died during the follow-up period. After adjustment for age, sex, thallium perfusion defects, and other confounders, failure to reach 85% of the age-predicted maximum heart rate was associated with increased risk of death (adjusted relative risk [RR], 1.84; 95% confidence interval [CI], 1.13-3.00; P=.01), as was a low chronotropic index (adjusted RR, 2.19; 95% CI, 1.43-3.44; P<.001). CONCLUSION:Among patients with known or suspected coronary disease, chronotropic incompetence is independently predictive of all-cause mortality, even after considering thallium perfusion defects. Incorporation of chronotropic response into the routine interpretation of stress thallium studies may improve the prognostic power of this test.