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We investigated the effects of positive end-expiratory pressure (PEEP) on carbon dioxide (CO2) elimination in a cross-over study of 14 patients whose lungs were ventilated after cardiac surgery. They initially received either 7.5 cm H2O PEEP or zero end-expiratory pressure and were then changed over to the other mode. We measured CO2 minute elimination (V̇CO2) and “efficiency,” a quantification of the shape of CO2 single-breath test (SBT-CO2), the plot of expired CO2 against expired volume. V̇CO2 and efficiency (and therefore the shape of SBT-CO2) were not significantly affected by PEEP. These results agree with findings in patients with acute lung injury, but are in contrast with those in an open-chest dog model, in which 7.5 cm H2O PEEP caused a 19% decrease in V̇CO2 and significant changes in SBT-CO2.During artificial ventilation, applying a positive pressure in expiration expands the lung and improves the uptake of oxygen, but there is a theoretical risk of reduced carbon dioxide elimination. We applied positive end-expiratory pressure to patients immediately after heart surgery and found that it has no effect on carbon dioxide elimination.