Chia-Hung Chen,1 Chih-Yen Tu,1 Wei-Chih Chen,2 Li-Kuo Kuo,3 Yao-Tung Wang,4 Pin-Kuei Fu,5 Shih-Chi Ku,6 Wen-Feng Fang,7 Chin-Ming Chen,8 Chih-Cheng Lai9 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 2Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 4Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; 5Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 6Division of Chest Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 8Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan; 9Department of Internal Medicine, Kaohsiung Veterans General Hospital, Tainan Branch, Tainan, TaiwanCorrespondence: Chih-Cheng Lai Email dtmed141@gmail.comObjective: The aim of this study was to compare the usefulness of cefoperazone-sulbactam and that of piperacillin-tazobactam in the treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP).Methods: This retrospective study included the adult patients receiving cefoperazone-sulbactam or piperacillin-tazobactam against HAP/VAP in nine hospitals in Taiwan from March 1, 2018 to May 30, 2019. Primary outcome was clinical cure rate.Results: A total of 410 patients were enrolled. Among them, 209 patients received cefoperazone-sulbactam and 201 patients received piperacillin-tazobactam. Overall, cefoperazone-sulbactam group had similar distribution of age, sex, or SOFA scores as piperacillin-tazobactam group. However, cefoperazone-sulbactam had higher comorbidity score and disease severity than piperacillin-tazobactam group (Charlson score: 6.5 ± 2.9 vs 5.7 ± 2.7, p < 0.001; APACHE II score: 21.4 ± 6.2 vs 19.3 ± 6.0, p = 0.002). Regarding clinical outcomes, no significant difference in clinical cure and failure rates was observed between cefoperazone-sulbactam and piperacillin-tazobactam group (clinical cure rate: 80.9% vs 80.1% and clinical failure rate: 17.2% vs 18.4%, p = 0.943). Moreover, no significant difference in clinical effectiveness and ineffectiveness rates was observed between cefoperazone-sulbactam and piperacillin-tazobactam group (clinical effective rate: 80.9% vs 80.6% and clinical ineffective rate: 17.7% vs 18.9%, p = 0.711). The all-cause mortality rates of the cefoperazone-sulbactam and piperacillin-tazobactam groups were similar (23.9% vs 20.9%, p = 0.48). After adjustment of Charlson score and APACHE II score, the similarities in these clinical outcomes did not change in overall patients and patients with HAP or VAP.Conclusion: For treating adult patients with nosocomial pneumonia, cefoperazone-sulbactam was as effective as piperacillin-tazobactam.Keywords: cefoperazone-sulbactam, hospital-acquired pneumonia, piperacillin-tazobactam, ventilator-associated pneumonia