9605 Background: Dexamethasone has a high therapeutic index for the prevention of chemotherapy-induced nausea and vomiting; however, the chronic use of high-dose glucocorticoids is associated with adrenal insufficiency. The objective of the present study was to assess the prevalence and associated factors of adrenal suppression after antiemetic dexamethasone therapy in cancer patients receiving chemotherapy. Methods: Patients who were scheduled to receive at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as one of antiemetics were enrolled. Patients with a suppressed baseline adrenal response before chemotherapy and those administrated corticosteroids within 6 months of study commencement were excluded. Results: Between October 2010 and August 2014, 481 patients receiving chemotherapy underwent the rapid ACTH stimulation test to assess eligibility; 350 of these patients were included in the final analysis. Fifty-six patients (16.0%) showed a suppressed adrenal response in the rapid ACTH stimulation test at 3 or 6 months after the first chemotherapy with dexamethasone as an antiemetic. Multivariate analysis revealed that the incidence of adrenal suppression was significantly associated with the duration of megestrol acetate use (P< 0.001). Adrenal suppression did not correlate with age, sex, performance status, primary tumor site, tumor stage, intent of first chemotherapy, emetic risk of first chemotherapy, chemotherapeutic agents used, or the dose and duration of dexamethasone. Conclusions: This large prospective study indicates that approximately 15% of cancer patients with a normal adrenal response showed suppressed adrenal responses after antiemetic dexamethasone therapy; this was particularly significant for patients co-treated with megestrol acetate.