Objective To investigate the application of sequential noninvasive ventilation (NIV) in weaning patients off mechanical ventilation after coronary artery bypass grafting (CABG). Methods From July 2007 to July 2009, 52 patients who underwent CABG with mechanical ventilation for no less than 24 hours and P/F Ratio lower than 150 mm Hg were divided into two groups with random number table. In the sequential NIV group (SNIV group), there were 19 patients including 16 males and 3 females whose ages were 69.26±8.10 years. In the prolonged mechanical ventilation group (PMV group), there were 33 patients including 28 males and 5 females whose ages were 70.06±7.09 years. Clinical data of these two groups were compared and the influence of NIV on the circulation and respiration of the patients were observed. Results The SNIV group weaned off mechanical ventilation earlier than the PMV group (26.46±3.66 h vs. 38.65±9.12 h, P=0.013). The SNIV group held shorter total ventilation time (29.26±21.56 h vs.54.45±86.57 h,P=0.016), ICU stay time (2.44±2.99 d vs. 4.89±7.42 d, P=0.028) and postoperative hospital time (10.82±4.31 d vs. 14.01±19.30 d, P=0.039) than the PMV group. Furthermore, the SNIV group had lower pneumonia rate (5.26% vs. 30.30%, P=0.033) and total postoperative complication rate (10.53% vs.45.45%, P=0.030) than the PMV group. However, there was no significant difference (Pgt;0.05) between the two groups in the successful weaning rate, repeated tracheal intubation rate, tracheotomy rate and mortality 30 days after operation. After NIV, SNIV group had no significant change in heart rate, central vein 〖CM(1585mm〗pressure, pulmonary arterial pressure and pulmonary arterial wedge pressure than the baseline value, while systolic pressure (129.66±19.11 mm Hg vs. 119.01±20.31 mm Hg, P=0.031), cardiacindex [3.01±0.30 L/(min.m2) vs. 2.78±0.36 L/(min.m2), P=0.043] and P/F Ratio (205.95±27.40 mm Hg vs. 141.33±9.98 mm Hg, P=0.001) were obviously elevated. Conclusion Sequential NIV is a effective and safe method to wean CABG patients off mechanical ventilation.