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Cefoperazone/sulbactam is a third-generation cephalosporin commonly used for severe infections. This case report presents a case of a 68-year-old woman who developed severe coagulation dysfunction and significant active bleeding after starting cefoperazone/sulbactam therapy following aortic dissection surgery. After discontinuing cefoperazone/sulbactam and administering vitamin K1, the patient’s coagulation function returned to normal, with no further abnormalities after changing antibiotics. On assessing causality of the adverse drug reaction, the Naranjo scale for cefoperazone/sulbactam was 6. This case highlights the risks of cefoperazone/sulbactam in patients with underlying conditions such as renal insufficiency and malnutrition, emphasising the need for carefully monitoring coagulation parameters and dose adjustment to reduce the occurrence of drug-induced coagulopathy and healthcare-associated complications. Additionally, this case serves as a reminder of the vital contributions that clinical pharmacists make in monitoring and managing medication therapy, stressing the importance of fostering collaboration between clinical pharmacists and other healthcare workers.