Background: Tropisetron, ondansetron, and granisetron are considered equally efficacious, supported by several international studies. However, there are interindividual variations in their metabolism that could affect efficacy. The clustering of such variations may change from one to another nation. Therefore, their equality must be validated in Turkish patients. The aim of this study was to compare their efficacies, side-effect profiles, and costs in the prophylaxis of emesis induced by moderate to high emetogenic chemotherapies. Methods: A total of 158 patients with a median age of 48 years, 115 (72.8 percent) female and 43 (27.2 percent) male, were included, respectively. Fifty-one, 61, and 46 patients were allocated to tropisetron (5 mg), ondansetron (8 mg), and granisetron (3 mg IV) in combination with 8 mg dexamethasone, which were continued 5 mg once a day, 8 mg b.i.d. and 1 mg b.i.d. PO for 5 days, respectively. Results: The complete response (CR) rates in the control of acute emesis were 80.4 percent with tropisetron, 72.1 percent with ondansetron, and 71.7 percent granisetron (p = 0.877). CR rates in delayed emesis (Days 2-5) were 68.6 percent, 68.9 percent, and 76.1 percent, respectively (p = 0.527). Rates of freedom from nausea in the same period were 37.3 percent, 35.9 percent, and 33.9 percent (p = 0.949). Nausea control rates, side-effect profile did not differ. However, headache seemed to be encountered higher (45.6 percent) in Turkish patients than others (3.9 9 percent). Tropisetron is the least expensive one ($ 95.3 per cycle) according to current prices in Turkey. Conclusions: There were no differences among the 3 serotonin antagonists with respect to efficacy and frequency of side-effects in our patients. Tropisetron is the least expensive at current prices. The choice may be based on other parameters, such as ease of administration and patient preference.