BACKGROUND Acinetobacter baumannii (AB) is a multidrug-resistant pathogen commonly associated with nosocomial infections. The resistance profile and ability to produce biofilm make it a complicated organism to treat effectively. Cefoperazone sulbactam (CS) is commonly used to treat AB, but the associated data are scarce. METHODS We conducted a systematic review of articles downloaded from Cochrane, Embase, PubMed, Scopus, and Web of Science (through June 2022) to study the efficacy of CS in treating AB infections. Our review evaluated patients treated with CS alone and CS in combination with other antibiotics separately. The following outcomes were studied: clinical cure, microbiological cure, and mortality from any cause. RESULTS We included 16 studies where CS was used for the treatment of AB infections. This included 11 studies where CS was used alone and 10 studies where CS was used in combination. The outcomes were similar in both groups. We found that the pooled clinical cure, microbiological cure, and mortality with CS alone for AB were 70%, 44%, and 20%, respectively. The pooled clinical cure, microbiological cure, and mortality when CS was used in combination with other antibiotics were 72%, 43%, and 21%, respectively. CONCLUSIONS CS alone or in combination needs to be further explored for the treatment of AB infections. There is a need for randomized controlled trials with comparator drugs to evaluate the drug's effectiveness.