Exercise testing with ventilatory expired gas analysis has proven to be a valuable tool for assessing patients with heart failure (HF). Peak oxygen consumption (peak VO2) continues to be considered the gold standard for assessing prognosis in HF. The minute ventilation--carbon dioxide production relationship (VE/VCO2 slope) has recently demonstrated prognostic significance in patients with HF, and in some studies, it has outperformed peak VO2. Two hundred thirteen subjects, in whom HF was diagnosed, underwent exercise testing between April 1, 1993, and October 19, 2001. The ability of peak VO2 and VE/VCO2 slope to predict cardiac-related mortality and hospitalization was examined. Peak VO2 and VE/VCO2 slope were demonstrated with univariate Cox regression analysis both to be significant predictors of cardiac-related mortality and hospitalization (P <.01). Multivariate analysis revealed that peak VO2 added additional value to the VE/VCO(2) slope in predicting cardiac-related hospitalization, but not cardiac mortality. The VE/VCO2 slope was demonstrated with receiver operating characteristic curve analysis to be significantly better than peak VO2 in predicting cardiac-related mortality (P <.05). Although area under the receiver operating characteristic curve for the VE/VCO2 slope was greater than peak VO2 in predicting cardiac-related hospitalization (0.77 vs 0.73), the difference was not statistically significant (P =.14). These results add to the present body of knowledge supporting the use of cardiopulmonary exercise testing in HF. Consideration should be given to revising clinical guidelines to reflect the prognostic importance of the VE/VCO2 slope in addition to peak VO2.