Abstract This study was performed to assess the efficacy and safety of olanzapine for the treatment of delirium in a Korean population. An open trial of olanzapine was conducted in Korean patients with delirium caused by multiple medicosurgical conditions. All subjects were evaluated by Delirium Rating Scale (DRS), which is known to be one of the most sensitive scales for delirium. In addition, other data for profiles of side-effects were collected and analyzed. Twenty patients were treated by olanzapine with doses of 5.9 ± 1.5 mg/day. The initial dose was 4.6 ± 0.9 mg/day and maximal dose of olanzapine was 8.8 ± 2.2 mg/day. The average duration of treatment was 6.6 ± 1.7 days and the day of maximal response was 3.8 ± 1.7 treated days. The scores of DRS were significantly improved from 20.0 ± 3.6 at the time of pretreatment to 9.3 ± 4.6 at the post-treatment. All subjects showed no definite serious side-effects including anticholinergic and extrapyramidal symptoms. Olanzapine treatment for patients with delirium was effective and safe. This newer drug may be a useful alternative agent to classical antipsychotics in the treatment of delirium.