The ventilatory strategy to adopt during cardiopulmonary bypass is still being debated. The rationale for using continuous positive airway pressure or mechanical ventilation would be to counteract alveolar collapse and improve ischemia phenomena and passive alveolar diffusion of oxygen. Although there are several studies supporting the hypothesis of a positive effect on oxygenation and systemic inflammatory response, the real clinical impact of ventilation during cardiopulmonary bypass is controversial. Furthermore, the biases present in the literature make the studies’ results nonunique in their interpretation.