Equine anesthesia is associated with greater morbimortality than other domestic species. An important factor in increasing anesthetic risk in horses is the development of extensive pulmonary atelectasis, which compromises gas exchange and respiratory mechanics. Hypoxemia is common during anesthesia and early evidence indicates that normalizing oxygenation intraoperatively may improve quality of recovery, a key aspect in anesthetic management of horses, especially those with orthopedic and abdominal pathology. A number of ventilatory protocols have been developed to assist lung function in anesthetized horses. Although some have shown improvement in oxygenation, these protocols have been linked to proinflammatory activity, impaired hemodynamic parameters, and importantly, are not tailored to the individual patient. Lung tissue opens and collapses as a viscoelastic system and thus is sensitive to the time that positive airway pressure is applied or removed. We propose a novel ventilation strategy that takes advantage of this knowledge using an: (i) extended inspiratory time to open collapsed lung and (ii) very short expiratory time to prevent lung collapse. Our time-controlled adaptive ventilation (TCAV) method has been shown highly effective in animal models of the acute respiratory distress syndrome (ARDS) and human ARDS patients. ARDS causes extensive atelectasis and thus may be similar to the problem encountered in the anesthetized horse. The TCAV method is both personalized and adaptive with changes in lung physiology, which is measured as changes in respiratory system compliance (CRS). Using the TCAV method the slope of the expiratory flow curve is a breath-by-breath measure of CRS and is used to set the expiratory time sufficiently short to prevent lung tissue collapse. Very low CRS as seen with atelectasis, will cause the lung to collapse rapidly, causing the slope of the expiratory flow to be steep, and resulting in a very short expiratory time. If CRS improves with lung recruitment the slope will be less steep, increasing the expiratory duration. If successful in horses, this technique could significantly improve lung function and might reduce perioperative anesthetic morbimortality. We have developed custom-made software designed to perform TCAV in anesthetized horses. We will leverage on our experience with this technique to conduct prospective crossover studies in experimental horses to refine the technique for this species. The aims of this proposal are to describe the ideal settings for TCAV in horses and to use this knowledge to compare the effects of the TCAV method and a conventional mode of ventilation on relevant cardiopulmonary outcomes. We hypothesize that TCAV in horses keeps the pulmonary alveoli recruited, maximizing oxygenation and improving overall cardiopulmonary function while reducing the lung’s proinflammatory response to mechanical ventilation, compared with a conventional ventilatory technique. If successful, we will translate this technique for use in different cohorts of equine patients in multicenter, collaborative efforts aimed to determine relevant short and long-term perioperative outcomes.