Abstract: Objective To investigate the value of Clinical Pulmonary Infection Score(CPIS)in guiding the treatment of tigecycline combined with cefoperazone sodium and sulbactam sodium for severe pneumonia patients. Methods Totally 60 patients with severe pneumonia were selected and randomly divided into two groups, with 30 cases in each group. Control group was treated with antibiotics according to the experience, and observation group was treated with antibiotics under the guidance of CPIS. The drug regimen in both groups was tigecycline combined with cefoperazone sodium and sulbactam sodium. The symptom disappearance rate, application time of antibiotics, levels of inflammatory indexes［C reactive protein(CRP), procalcitonin(PCT), white blood cell count(WBC)］ and adverse reactions were compared between the two groups. Results After 2 weeks of treatment, the fever symptoms disappeared in both groups, and there were no significant differences in the disappearance rate of pulmonary rales and expectoration between the two groups(P>0.05). The application time of antibiotics in the observation group was(7.38±2.66)days, which was significantly shorter than(9.82±2.89)days in the control group(t=3.403, P=0.001). The levels of CRP, PCT and WBC in both groups after treatment were significantly lower than those before treatment(P<0.05). The incidence of adverse reactions in the observation group was significantly lower than that in the control group(P<0.05). Conclusion Under the guidance of CPIS, tigecycline combined with cefoperazone sodium and sulbactam sodium is safe and effective in the treatment of severe - pneumonia patients, which can shorten the medication time and relieve the symptoms of patients.