Objective To explore the effect of continuous aspiration of subglottic secretion at different negative pressure levels on mechanical ventilation. Methods Toally 142 patients were randomized by way of lottery into the control group (n=70) and the experiment group ( n = 72 ): the control group received continuous negative pressure aspiration of subglottic secretion at a negative pressure of 60 mmHg while the experiment group did 30~40 mmHg for grade I of the sticky secretion , 40~60 mmHg for gradeⅡ~Ⅲof the sticky secretion, respectively. The two groups were compared in terms of the rate of ventilator associated pneumonia (VAP), airway mucosal injury and cough. Result There was no significant difference in the rate of ventilator associated pneumonia (P>0.05), but the rates of airway mucosal injury and cough were lower in the experiment group than those of the control group (P < 0.05). Conclusion It is reasonable to choose different negative pressure levels based on stickiness of the secretions for mechanical ventilation, for it can prevent the ventilator associated pneumonia and airway mucosal injury.