Cardiopulmonary variables, particularly peak oxygen consumption (peak VO2) corrected for total and lean body weight, have been confirmed to predict prognosis in patients with chronic systolic heart failure (HF). Only limited data are available on the prognostic ability of maximal oxygen (O2) pulse, an indicator of stroke volume and arteriovenous O2 difference, especially when corrected for lean body mass. Cardiopulmonary exercise tests were performed in 209 consecutive patients with mild-to-moderate HF (mean ejection fraction 23%), followed for 19 ± 12 months to determine the impact of maximal O2 pulse in relation to other cardiopulmonary variables on major clinical events (13 cardiovascular deaths and 15 urgent transplantations). Compared with patients with clinical events, those without major events had a higher peak O2 pulse (11.4 ± 4.1 vs 9.2 ± 2.3 ml/beat, p <0.0001) and body fat-adjusted peak O2 pulse (15.6 ± 5.6 vs 11.9 ± 3.4 ml/beat, p <0.0001). In multivariate analysis, a low peak O2 pulse was the strongest independent predictor of clinical events (chi-square 10.5, p <0.01). Although peak O2 pulse was a stronger predictor for clinical events than any other exercise cardiopulmonary variable, including peak VO2, peak VO2 lean (defined as the VO2 corrected for lean body mass), and percentage of predicted peak VO2, this relation was further strengthened by correcting peak O2 pulse for percent body fat (chi-square 12.4, p <0.001). In most subgroups (including women, obese subjects, those receiving β blockers, and those with class III HF), peak O2 pulse lean was similar to or superior to peak VO2 lean for predicting major clinical events. Especially in patients who were class III HF and who were receiving β blockers, peak VO2 (cutoff 14 ml/kg/min) poorly predicted prognosis; risk stratification was best with peak O2 pulse lean (cutoff 14 ml/beat). These data indicate the potential usefulness of peak O2 pulse and lean body mass–adjusted O2 pulse for predicting prognosis in patients with systolic HF.