Purpose: Olanzapine has antiemetic activity for chemotherapy-induced nausea and vomiting (CINV). The purpose of this retrospective study is to evaluate the efficacy of olanzapine for prevention of CINV in patients with severe nausea resistant to standard antiemetic regimen for highly emetogenic chemotherapy (HEC). Methods: Olanzapine was administered in twenty gynecological cancer patients receiving HEC. They had grade 3 nausea (CTCAE ver.4.0) for the acute (24 hours postchemotherapy) and/or delayed (24-120 hours postchemotherapy) period despite the combined use of 5-HT3 receptor antagonist, NK-1 receptor antagonist, and dexamethasone. Oral olanzapine (5 mg/day) was administered on day -1 prior to chemotherapy and continued for 7 days in combination with standard antiemetic regimen. The nausea control rate (grade 0-1) with olanzapine were evaluated. Results: The nausea control rate improved from 30% to 95% for the acute period, 0% to 95% for the delayed period, and 0% to 90% for the overall period. In each period, the nausea control rate improved significantly (p≤0.001). Grade 0-1 sleepiness was observed but there were no grade 3 or 4 toxicities. Conclusion: In this study, olanzapine combined with the standard antiemetic regimen had good antiemetic activity at both acute and delayed period in most of chemotherapy-naive patients receiving HEC. The efficacy of olanzapine suggested additional improvement in the control of severe CINV resistant to standard antiemetic regimen for HEC.