Objective To compare the effect of three endotracheal tube cuff shapes on preventing leakage of subglottic secretions with different viscosity, and to provide reference for airway management. Methods Nine trachea models were made by using 20-mL syringe and divided into three groups, then conical-shaped cuff, cylindrical-shaped cuff, and spindle-shaped cuff tracheal tubes were inserted into the trachea model placed in a vertical position at a fixed height. The cuff of each tube was inflated until reaching a pressure ranging between 29 and 30 cmH2O. Five milliliters of subglottic secretions with different viscosity (watery, thick, and gel-like), which were suctioned from ventilated patients, were poured above the cuff and the volume of fluid leaking around the tube was collected and quantified at 30 min, 60 min,120 min, 240 min, 360 min， and 480 min. The experiments repeated 10 times for each viscosity of the secretions. Results Generalized estimating equations showed that there were significant differences in the volume of leakage, regardless of different viscosity, for three cuff shapes of tubes over time (all P<0.05). Conclusion The conical-shaped cuff tube is the most effective in ensuring appropriate tracheal sealing, followed by the cylindrical-shaped cuff, and the worst is the spindle-shaped cuff. Peri-cuff leak might happen in all tracheal cuff shapes over time. It is recommended that cylindrical-shaped cuff tube with flushing functions or conical-shaped cuff tube should be utilized, in addition to timely flushing and suctioning subglottic secretions, to prevent ventilator-associated pneumonia.