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To determine whether the application of continuous aspiration of subglottic secretions (CASS) is associated with a decreased incidence of ventilator-associated pneumonia (VAP).Prospective clinical trial.Cardiothoracic ICU (CTICU) of Barnes-Jewish Hospital, St. Louis, a university-affiliated teaching hospital.Three hundred forty-three patients undergoing cardiac surgery and requiring mechanical ventilation in the CTICU.Patients were assigned to receive either CASS, using a specially designed endotracheal tube (Hi-Lo Evac; Mallinckrodt Inc; Athlone, Ireland), or routine postoperative medical care without CASS.One hundred sixty patients were assigned to receive CASS, and 183 were assigned to receive routine postoperative medical care without CASS. The two groups were similar at the time of randomization with regard to demographic characteristics, surgical procedures performed, and severity of illness. Risk factors for the development of VAP were also similar during the study period for both treatment groups. VAP was seen in 8 patients (5.0%) receiving CASS and in 15 patients (8.2%) receiving routine postoperative medical care without CASS (relative risk, 0.61%; 95% confidence interval, 0.27 to 1.40; p = 0.238). Episodes of VAP occurred statistically later among patients receiving CASS ([mean ± SD] 5.6 ± 2.3 days) than among patients who did not receive CASS (2.9 ± 1.2 days); (p = 0.006). No statistically significant differences for hospital mortality, overall duration of mechanical ventilation, lengths of stay in the hospital or CTICU, or acquired organ system derangements were found between the two treatment groups. No complications related to CASS were observed in the intervention group.Our findings suggest that CASS can be safely administered to patients undergoing cardiac surgery. The occurrence of VAP can be significantly delayed among patients undergoing cardiac surgery using this simple-to-apply technique.