Mechanical ventilation is usually achieved by active lung inflation during inspiration and passive lung emptying during expiration. By contrast, flow-controlled expiration (FLEX) ventilation actively reduces the rate of lung emptying by causing linear gas flow throughout the expiratory phase. Our aim was to evaluate the effects of FLEX on lung compliance and gas exchange in anesthetized horses in dorsal recumbency. 8 healthy horses. All animals were anesthetized twice and either ventilated beginning with FLEX or conventional volume-controlled ventilation in a randomized, crossover design. Total anesthesia time was 3 hours, with the ventilatory mode being changed after 1.5 hours. During anesthesia, cardiac output (thermodilution), mean arterial blood pressures, central venous pressure, and pulmonary arterial pressure were recorded. Further, peak, plateau, and mean airway pressures and dynamic lung compliance (Cdyn) were measured. Arterial blood gases were analyzed every 15 minutes. Data were analyzed using ANOVA (P < 0.05). FLEX ventilation resulted in significantly higher arterial oxygen partial pressures (521 vs 227 mm Hg) and Cdyn (564 vs 431 mL/cm H2O) values compared to volume-controlled ventilation. The peak and plateau airway pressure were lower, but mean airway pressure was significantly higher (4.8 vs 9.2 cm H2O) in FLEX ventilated horses. No difference for cardiovascular parameters were detected. The results of this study showed a significant improvement of the Pao2 and Cdyn without compromising the cardiovascular system when horses were ventilated by use of FLEX compared to conventional ventilation.