Objective: To discuss the influence of ABCDE analgesic and sedative strategy on breathing mechanics of severe mechanical ventilation (MV) patients. Methods: The severe MV patients were divided into the observation group and the control group according to the ICU hospitalization sequence. The control group adopted routine analgesic and sedative nursing strategy while the observation group adopted ABCDE analgesic and sedative nursing strategy. The changes of breathing mechanics parameter before intervention (T0) and on the first day (T1), third day (T2), fifth day (T3) and seventh day (T4) after intervention as well as treatment prognosis of the patients of the two groups were collected and compared. Results: As indicated by the comparison of breathing mechanics parameters of the two groups at different time points, airway peak pressure (Ppeak), platform pressure (Pplat), dynamic compliance (Cdny) and tidal volume (VT) at T2–T4 of the observation group were improved evidently in contrast to those at T0; and the improvement effect was better than that of the control group in the corresponding period. The differences were of statistical significance (P<0.05). As indicated by the further repeated measurement variance analysis results, inter-group effect, time effect and interaction effect of the above indexes at different time were of statistical significance. According to the comparison of various treatment prognosis parameters, MV time and ICU hospitalization time of the observation group were shorter than those of the control group. The 28-day survival rate of the observation group was evidently higher than that of the control group. The differences were of statistical significance (P<0.05). Conclusion: ABCDE analgesic and sedative strategy is a safe and effective intervention strategy. It can effectively reduce the airway pressure of severe MV patients, increase the tidal volume and increase the lung dynamic compliance. It plays a positive role in promoting the treatment prognosis.