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 β-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.