Abstract: Objective To investigate the efficacy and safety of aerosol inhalation of polymyxin B in the treatment of ventilator-associated pneumonia (VAP) caused by multiple drug resistance organisms (MDROs). Methods Head-to-head comparison was conducted to investigate the efficacy and safety of aerosol inhalation of polymyxin E (group A), intravenous injection of polymyxin E (group B), and aerosol inhalation of polymyxin B (group C) in the treatment of VAP caused by MDROs. Results Aerosol inhalation of polymyxin B had an effective rate of 76.7%, which was significantly better than aerosol inhalation of polymyxin E and intravenous infusion of polymyxin E (P<0.05). The average effective treatment time was (7.3±2.1) days. After aerosol inhalation of polymyxin B, the patients presented remarkably increased levels of serum prealbumin(PA), procalcitonin(PCT), and tumor necrosis factor (TNF-α), as well as CD4⁺and CD4⁺/CD8⁺, compared with those receiving aerosolized polymyxin E and intravenously infused with polymyxin E (P<0.05). Aerosol inhalation of polymyxin B had good safety, without severe adverse reactions. Conclusions Aerosol inhalation of polymyxin B is more effective than intravenous injection of polymyxin E and aerosol inhalation of polymyxin E in the treatment of VAP caused by MDROs. The safety is comparable and has significant clinical value.