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Abstract: Background: Increased end-tidal oxygen (ET-O2) and decreased end-tidal carbon dioxide (ET-CO2) gas tensions are noninvasively measurable correlates of ventilatory inefficiency, leading to increased ventilatory requirements relative to gas exchange among patients with chronic heart failure (CHF). We investigated the prognostic value of ET-O2 and ET-CO2 as predictors of CHF mortality. Methods: We measured resting ET-O2 and ET-CO2 electrochemically in 134 patients with symptomatic CHF in the supine position. We used Kaplan-Meier analysis, Cox proportional hazard models, and receiver operating characteristic curves to test our hypothesis. Results: At a median follow-up of 16.5 months, 32 patients had died. ET-O2 levels were increased (P = .001) and ET-CO2 levels decreased (P = .002) with increased New York Heart Association class (I–IV). Survivors showed lower ET-O2 (121 vs 118 mm Hg; P = .021) and higher ET-CO2 (33.2 vs 32.1 mm Hg; P = .032) levels than nonsurvivors. Patients with ET-O2 values ≥121 mm Hg and/or ET-CO2 values <31 mm Hg had an increased risk of death with hazard ratios of 2.93 (95% confidence interval [CI], 1.43–6.01) and 2.47 (95% CI, 1.23–4.97), respectively. Kaplan-Meier estimates for follow-up mortality with ET-O2 ≥121 mm Hg and/or ET-CO2 <31 mm Hg were 83.8% (vs 60.1%; P = .0014) and 80.3% (vs 60.2%; P = .0061), respectively. Areas under the receiver operating characteristic curves for prediction of death with ET-O2 and ET-CO2 were both significant and similar to that of echocardiographic left ventricular function. Conclusions: In CHF, high levels of ET-O2 and low levels of ET-CO2 are associated with increased mortality. We suggest that the measurements may be useful prognostic markers for risk stratification. [Copyright &y& Elsevier]