Ventilatory efficiency is commonly defined as the level of ventilation V̇E at a given carbon dioxide output (V̇CO2). The slope of the V̇E versus V̇CO2 relationship and the lowest V̇E/V̇CO2 are two ventilatory efficiency indices that can be measured during cardiopulmonary exercise testing (CPET). A possible CPET mode dependency for these indices was evaluated in healthy men and women. Also evaluated was the relationship between these two indices as, in theory, V̇E/V̇CO2 falls hyperbolically towards an asymptote that numerically equals the V̇E versus V̇CO2 slope at exercise levels below the ones that cause respiratory compensation for metabolic acidosis. Twenty-eight healthy subjects (14 men) underwent treadmill and cycle ergometer CPET on different days. Ventilation and the gas fractions for oxygen and CO2 were measured with a vacumed metabolic cart. In men, paired t-test analysis failed to find a mode difference for either ventilatory efficiency index but the opposite was true in the women as each woman had higher values for both indices on the treadmill. For men, the lowest V̇E/V̇CO2 was larger than the V̇E versus V̇CO2 slope by 1·3 on the treadmill and 0·8 on the cycle ergometer. The corresponding values for women were 1·7 and 1·4. We conclude that in healthy subjects, women, but not men, demonstrate a mode dependency for the two ventilatory efficiency indices investigated in this study. Furthermore, our results are consistent with the theoretical expectation that the lowest V̇E/V̇CO2 has a numerical value just above the asymptote of the V̇E/V̇CO2 versus V̇CO2 relationship.