Abstract Perospirone is a recently developed atypical antipsychotic with potent serotonin 5-HT2 and dopamine D2 antagonist activity. Other atypical antipsychotics including risperidone, quetiapine and olanzapine have been widely used for treatment, not only for schizophrenia symptoms but also for delirium, because of their low potential to induce extrapyramidal disturbances. In the present study the effectiveness and safety of perospirone in patients with delirium are described. Thirty-eight patients with DSM-IV delirium were given open-label perospirone. To evaluate the usefulness of perospirone, scores from 13 severity items of the Delirium Rating Scale-Revised-98 were assessed. Data were gathered from October 2003 to September 2004. Perospirone was effective in 86.8% (33/38) of patients, and the effect appeared within several days (5.1 ± 4.9 days). The initial dose was 6.5 ± 3.7 mg/day and maximum dose of perospirone was 10.0 ± 5.3 mg/day. There were no serious adverse effects. However, increased fatigue (15.2%), sleepiness (6.1%), akathisia (3.0%) and a decline in blood pressure (3.0%) were observed. It is proposed that perospirone may be another safe and effective atypical antipsychotic drug for the treatment of delirium symptoms in hospitalized patients. This is a preliminary open trial, and further randomized double-blind placebo-controlled tests are needed.