【Abstract】 Objective To investigate the effect of invasivenoninvasive sequential mechanical ventilation on plasma atrial natriuretic peptide (ANP) and B Nterminal pro brain natriuretic peptide (NTproBNP) in patients with severe pneumonia and respiratory failure. Methods 98 patients with severe pneumonia complicated with respiratory failure were divided into the sequential group (invasivenoninvasive sequential mechanical ventilation) and the routine group (traditional invasive mechanical ventilation) according to different methods of mechanical ventilation. The changes of indexes of blood gas analysis, respiratory rate (RR) and heart rate (HR) before and after treatment were compared between the two groups. The total time of mechanical ventilation, duration of ventilation, length of intensive care unit (ICU) stay, total hospitalization time, the incidence of ventilatorassociated pneumonia (VAP), the success rate of weaning and inhospital mortality rates in two groups were statistically analyzed. After 3 days of treatment, the peripheral blood of patients was collected to determine and compare serum related inflammatory factors and cardiac injury associated indexes. Results After treatment, RR, HR and partial pressure of carbon dioxide (PaCO2) in the two groups were significantly decreased, while partial pressure of oxygen (PaO2) and pH were increased significantly (P＜005). The above indexes showed no significant differences between the two groups (P＞005). The total time of mechanical ventilation, duration of invasive ventilation, length of ICU stay and total hospitalization time were significantly shorter, the incidence rate of VAP and inhospital mortality rate were significantly lower, and the success rate of weaning was significantly higher in the sequential group than the routine group (P＜005). 3 days after treatment, levels of serum interleukin4 (IL4), interleukin6 (IL6), interleukin10 (IL10), tumor necrosis factor α (TNFα), plasma atrial natriuretic peptide (ANP), type B Nterminal natriuretic peptide (NTproBNP) and troponin I (cTnI) were significantly lower in the sequential group than the routine group (P＜005). Conclusion The therapeutic effect of sequential invasivenoninvasive mechanical ventilation is relatively better in the treatment of severe pneumonia with respiratory failure. The regimen can significantly shorten the duration of invasive ventilation and reduce the levels of ANP and NTproBNP and cardiac function injury. It also can significantly reduce the inflammatory response, the incidence of VAP and mortality rate.