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Aspiration of secretions containing bacterial pathogens into the lower respiratory tract is the main cause of ventilator-associated pneumonia. Endotracheal tubes with subglottic secretion drainage can potentially reduce this and, therefore, the incidence of ventilator-associated pneumonia. New evidence on subglottic secretion drainage as a preventive measure for ventilator-associated pneumonia has been recently published and to consider the evidence in totality, we conducted an updated systematic review and meta-analysis.We searched computerized databases, reference lists, and personal files. We included randomized clinical trials of mechanically ventilated patients comparing standard endotracheal tubes to those with subglottic secretion drainage and reporting on the occurrence of ventilator-associated pneumonia. Studies were meta-analyzed for the primary outcome of ventilator-associated pneumonia and secondary clinical outcomes.We identified 13 randomized clinical trials that met the inclusion criteria with a total of 2442 randomized patients. Of the 13 studies, 12 reported a reduction in ventilator-associated pneumonia rates in the subglottic secretion drainage arm; in meta-analysis, the overall risk ratio for ventilator-associated pneumonia was 0.55 (95% confidence interval, 0.46–0.66; p < .00001) with no heterogeneity (I2 = 0%). The use of subglottic secretion drainage was associated with reduced intensive care unit length of stay (−1.52 days; 95% confidence interval, −2.94 to −0.11; p = .03); decreased duration of mechanically ventilated (−1.08 days; 95% confidence interval, −2.04 to −0.12; p = .03), and increased time to first episode of ventilator-associated pneumonia (2.66 days; 95% confidence interval, 1.06–4.26; p = .001). There was no effect on adverse events or on hospital or intensive care unit mortality.In those at risk for ventilator-associated pneumonia, the use of endotracheal tubes with subglottic secretion drainage is effective for the prevention of ventilator-associated pneumonia and may be associated with reduced duration of mechanical ventilation and intensive care unit length of stay.