Abstract: OBJECTIVE To evaluate the cost-effectiveness of cefotiam and cefoperazone/sulbactam in treating respiratory system infections with renal insufficiency patients and to provide reference for clinical rational use of drugs in this special group. METHODS In regard to the use of antibiotics in hospitalized patients with renal insufficiency from January 2017 to December 2017, a retrospective, multi-center cohort study was conducted in three large-scale general hospitals in Anhui province. Based on treatment effects and adverse drug reactions, cost-minimization analysis was used to evaluate the top two cephalosporins (cefotiam vs cefoperazone/sulbactam) for pharmacoeconomic evaluation. RESULTS Eighty-five patients treated with cefotiam and eighty-five with cefoperazone/sulbactam were included. There was no significant difference in the clinical effective rate between the two groups (92.94% vs 95.29%, P=0.746). No significant adverse reactions were found during hospitalization. A cost-minimization analysis was adopted for economic evaluation. Medical costs was lower in cefotiam group for respiratory system infections with renal insufficiency patients(437.46 vs 682.28, P<0.001). CONCLUSION Cefotiam is more economical than cefoperazone/sulbactam in treating respiratory system infections with renal insufficiency patients.