BACKGROUND: Clearing subglottic secretions has been proved to reduce ventilator-associated pneumonia. A manual method named the rapid flow expulsion maneuver was developed to clear subglottic secretions. This study evaluates its safety and effectiveness and analyzes the influential factors. METHODS: This study was composed of 2 parts. In an in vitro study, secretions were instilled directly to the area above the cuff in an intubated tracheal model. Secretions were expelled by the rapid flow expulsion maneuver with different volumes and peak flows in 3 tracheal positions (0, 15, and 30 degrees). At each tracheal position, the maneuver was repeated twice, unless secretions above the cuff were <0.5 mL. In an in vivo study, subglottic secretions were suctioned via subglottic secretion drainage and then were cleared by the rapid flow expulsion maneuver. After the initial maneuver, methylene blue (2 mL) was instilled above the cuff, and the maneuver was performed again. The subject's sputum color was then recorded over 24 h. RESULTS: In the in vitro study, no aspiration was observed in the 277 maneuvers completed. Subglottic secretions were visibly expelled in 167 of 277 maneuvers (60.3%), and the median clearance efficiencies of the 3 consecutive maneuvers were 39.6, 6.3, and 0.4%. In the 108 first maneuvers, 93 (86.1%) produced visible secretions. Multiple linear regression models were used to identify predictors of clearance efficiency: tracheal position (P < .001), flow (P = .041), and secretion viscosity (P = .017). In the in vivo study, 77 rapid flow expulsion maneuvers were completed after suctioning via subglottic secretion drainage in 16 subjects, and the maneuvers collected 221.5 mL of secretions. No aspiration was observed over 24 h. CONCLUSIONS: The rapid flow expulsion maneuver was safe and effective to clear subglottic secretions. The first maneuver was the most effective to expel the majority of secretions. Supine position and high peak flow improved the clearance efficiency.