Objective To summarize and evaluate the application effects of the best evidence of aspiration pre- vention in adult patients with mechanical ventilation. Methods The best evidence for the prevention of aspiration in patients with mechanical ventilation was developed into an evidence-based practice plan by using the method of evidence-based nursing. After baseline review，obstacle factor analysis，and construction of the best evidence applica- tion strategy，the best evidence was implemented in the emergency intensive care unit of a tertiary hospital in Hangzhou from October 1 to November 20，2022. The incidence of aspiration in patients before and after evidence- based practice，the implementation rate of review indicators，and the scores of emergency intensive care unit nurses on the knowledge questionnaire of aspiration prevention and management in patients with mechanical ventilation were compared. Results Finally，23 evidences were included and 19 review indicators were formed. After evidence- based practice，the incidence of aspiration in patients with mechanical ventilation decreased from 21.43% to 6.67%，and the incidence of ventilator-associated pneumonia （VAP） decreased from 28.57% to 6.67%. Except for indicator 10 and 19，the implementation rate of the other review indicators increased to more than 90%. The score of nurses’ questionnaire on knowledge of aspiration prevention and management in patients with mechanical ventilation increased from （78.04±1.58） points to （91.04±0.98） points，and the difference was statistically significant （t=-11.879，P＜0.001）. Conclusion Applying the best evidence to clinical nursing practice is conducive to reduce the incidence of aspiration in patients with mechanical ventilation，improve the quality of clinical nursing.