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This study aims to assess the in vitro activity of different samples of cefoperazone/sulbactam (CFP/SUL) against multidrug-resistant organisms (MDROs). Clinical isolates of extended-spectrum &#946;-lactamase (ESBL)-<i>Escherichia coli</i>, ESBL-<i>Klebsiella pneumoniae</i>, carbapenem-resistant <i>Acinetobacter baumannii</i> (CR-AB), and carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CR-PA) were collected. The minimum inhibitory concentration (MIC) and time-killing methods were used to assess and compare the in vitro activities of different samples of cefoperazone/sulbactam (CFP/SUL) against these MDROs. For ESBL-<i>E. coli</i>, ESBL-<i>K. pneumoniae</i>, and CR-PA, product C had smaller variations than product A and B (<i>p</i> &lt; 0.05). For CR-AB, product B had the largest variation compared to the other two products (<i>p</i> &lt; 0.05). In the time-killing studies, significant differences among the products when used at 16/16 &#181;g/mL were noted for ESBL-<i>E. coli</i>, ESBL-<i>K. pneumoniae</i>, and CR-AB isolates. In conclusion, this study demonstrated the significantly different activity of different products of CFP/SUL against MDROs.