The present study was designed to identify the effect of positive end expiratory pressure (PEEP) and the ideal pulmonary tidal volume to ventilate animals with a surgically produced bronchopleural fistula, aiming to reduce fistula output without affecting gas exchange. Hemodynamic and respiratory assessment of gas exchange was obtained in five, healthy, young, mechanically ventilated Large White pigs under volume controlled ventilation with FiO2 of 0.4 and an inspiration:expiration ratio of 1:2, keeping respiratory rate at 22 cpm. A bronchopleural fistula was produced by resection of the lingula. Underwater seal drainage was installed and the thorax was hermetically closed. Gas exchange and fistula output were measured with the animals ventilated sequentially with tidal volumes of 4 ml/kg, 7 ml/kg and 10 ml/Kg alternating zero of positive end expiratory pressure (ZEEP) and PEEP of 10 cmH2O, always in the same order. These findings are attributed to reduced alveolar ventilation and ventilation/perfusion abnormalities and were attenuated with larger tidal volumes. PEEP increases air leak, even with low volume (of 2.0 ± 2.8mL to 31 ± 20.7mL; p= 0.006) and decreases alveolar ventilation in all tidal volumes. Alveolar ventilation improved with larger tidal volumes, but increased fistula output (10 mL/kg - 25.8 ± 18.3mL to 80.2 ± 43.9mL; p=0.0010). Low tidal volumes result in hypercapnia (ZEEP - Toneloto MGC, Terzi RGG, Silva WA, Moraes AC, Moreira MM 83.7± 6.9 mmHg and with PEEP 10 - 93 ± 10.1mmHg) and severely decreased arterial oxygen saturation, about of 84%. The tidal volume of 7 ml/Kg with ZEEP was considered the best tidal volume because, despite moderate hypercapnia, arterial oxygen saturation is sustained around 90%, alveolar ventilation improves and the fistula output is reduced when compared with a tidal volume of 10ml/Kg. A low tidal volume results in hypercapnia and severe desaturation. Finally, at any tidal volume, PEEP increases the fistula leak and decreases alveolar ventilation.20254-260