Cardiac output during right-sided heart catheterization is an important variable for patient selection of advanced therapies (cardiac transplantation and left ventricular assist device implantation). The Fick method to determine cardiac output is commonly used and typically uses estimated oxygen consumption (VO₂) from 1 of 3 published empirical formulas. However, these estimation equations have not been validated in patients with heart failure and reduced ejection fraction (HFrEF). The objectives of the present study were to determine the accuracy of 3 equations for estimating VO₂ compared with direct measurement of VO₂ and determine the extent clinically significant error occurred in calculating cardiac output of patients with HFrEF. Breath-by-breath measurements of VO₂ from 44 patients who underwent cardiac catheterization (66% men; age, 65 ± 11 years, left ventricular ejection fraction, 22 ± 6%) were compared with the derived estimations of LaFarge and Miettinen, Dehmer et al, and Bergstra et al. Single-sample t tests found only the mean difference between the estimation of LaFarge and Miettinen and the measured VO₂ to be nonsignificant (−10.3 ml/min ± 6.2 SE, p = 0.053). Bland-Altman plots demonstrated unacceptably large limits of agreement for all equations. The rate of ≥25% error in the equations by LaFarge and Miettinen, Dehmer et al, and Bergstra et al occurred in 11%, 23%, and 45% of patients, respectively. Misclassification of cardiac index derived from each equation for 2 clinically important classifications: cardiogenic shock–21%, 23%, and 32% and hypoperfusion–16%, 16%, and 25%; respectively. In conclusion, these findings do not support the use of these empiric formulas to estimate the VO₂ at rest in patients with HFrEF who underwent right-sided heart catheterization.