Objective To investigate the effect of comprehensive chest physical therapy on weaning trend of patients on mechanical ventilation therapy. Methods Totally, sixty patients on mechanical ventilation therapy in the ICU were randomly divided into an intervention group （n=32） and a control group （n=28）.The control group received routine treatment and the intervention group received comprehensive chest physical therapy.Changes in rapid shallow breathing index （RSBI）, and oxygenation index （OI）, incidence rate of atelectasis and length of mechanical ventilation therapy were collected and analyzed for the two groups. Results There were significant differences in RSBI and OI, between the two groups on the 3 rd day of intervention （P＜0.01 for both）; the incidence rate of atelectasis in the intervention group was lower than in the control group, and the duration of mechanical ventilation in the former were shorter than in the latter, though no significant differences were found (P＞0.05 for both). Conclusion Comprehensive chest physical therapy based on disease assessment can effectively improve pulmonary oxygenation function and reduce pulmonary complications, which may have a positive effect on accelerating weaning and needs to be confirmed through further research.