Background: Delirium exemplifies the interface between medicine and psychiatry. The mainstay of treatment of delirium are the antipsychotic drugs. These are efficacious and safe for the treatment of delirium. In the last decade the use of second generation antipsychotics has been advocated at the expense of the classical drugs, particularly haloperidol. We thus aimed to compare the outcome of delirium treatment in a large, university-affiliated general hospital. Methods: We used retrospective medical charts analysis over a one-year period. Those included were all patients who had been admitted to an acute internal medicine ward for delirium or who had developed delirium during their hospital stay. Results: 191 patients' records were analysed. Mean age for the group was 78.8 1.1 years. There were 108 males (56.5%) and 83 (43.5%) female patients. The most frequent co-morbid psychiatric diagnosis was that of dementia (106; 56%). The most common physical conditions were: cardiovascular (75 patients) and sepsis (24 patients). Patients suffering from delirium were mostly treated with an antipsychotic: 147 (77%) were treated either with risperidone (73 patients) or classical antipsychotics (74 patients). The most frequently used classical antipsychotic was haloperidol (59/74). Mean risperidone dose was 1.7 0.4 mg/daily. Mean haloperidol dose was 7.8 1.9 mg/daily. Mean duration of antipsychotic treatment was 3.8 days for the classical antipsychotics group and 2.6 for the risperidone group (p = 0.04). In the untreated group, mean delirium episodes lasted 5.6 days - significantly longer than that of either treated groups, p = 0.02. Mean hospital stay (days) for the group was 12.8 1.4. In the risperidone treated group the mean stay was 10.8 days while in the classical antipsychotics group it was 13.5 and in the untreated group it was 15.5 (p = 0.008). Fourteen patients (7.3%) died during the delirium episode: 10 untreated, 3 treated by classical antipsychotics and 1 risperidone treated (p = 0.04). The majority of patients (65%) were discharged to the community. Conclusions: The present study adds to the growing body of evidence favoring risperidone as the drug of choice for the treatment of delirium. However, due to the limitations inherent in a retrospective analysis, prospective large-scale trials are needed to support this recommendation.