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Objective. The efficacies of the selective 5-hydroxytryptamine3 (5-HT3) antagonists- - ramosetron (0.3 mg) and granisetron (3 mg) in treating acute chemotherapy-induced digestive system dysfunction were compared. Methods. A total of 111 patients were enrolled in a single-blind, randomized crossover study; with data from 98 were used to assess efficacy and data from 110 to assess the safety profile. Ramosetron or granisetron was given intraveneously 15 min before chemotherapy. Results. The ability of ramosetron to prevent emesis, nausea and anorexia was similar to granisetron during the first 6 h following the administration of chemotherapy, cisplatin or doxorubicin. However, during the first 24 h after chemotherapy, significant differences between ramosetron and granisetron appeared: emetic episode (P=0.068), nausea (P=0.006), and anorexia (P=0.048) remained lower in ramosetron-treated patients. The safety profile of ramosetron was similar to that of granisetron and adverse events in both groups were generally mild and transient. Conclusion. Ramosetron is more potent and longer-lasting than granisetron in preventing chemotherapy-induced digestive disturbances.