Postoperative delirium (POD) is a complication that can occur in patients of any age undergoing major surgery. Due to the high incidence of delirium morbidity and mortality, it is important to identify and treat delirium quickly and successfully. Although many organic, surgical and psychiatric risk factors are recognized as putative causes of delirium, heroin withdrawal is not yet well defined and evaluated in the prevention and treatment of POD. We report a case report of a multi-drug addicted patient, without any other psychiatric comorbidity, suffering from heroin-withdrawal POD after urgent major cardiac surgery, successfully treated with clonazepam orally after conventional therapy failure. At the time of discharge, POD was completely solved and without further complications, psychiatric therapy was further reduced just to a low dose of clonazepam and the patient was referred to a specialized drug abuse center. The reported case suggests that clonazepam may be considered a valid option in case of heroin-withdrawal POD after conventional treatments failure.