Background:Chemotherapy induced nausea and vomiting (CINV) is one of the most disturbing side-effects in children receiving highly emetogenic chemotherapy. We aimed to assess whether the addition of an antiemetic cocktail containing midazolam and diphenhydramine to granisetron plus dexamethasone combination could ameliorate CINV in this study.Patients and Methods:A total of 23 children aged between 1 and 16 years to receive cisplatin containing chemotherapy in our clinic were included in this study from April 2007 to April 2008. 76 cycles in 23 patients were randomly assigned to receive either antiemetic regimen 1 or antiemetic regimen 2. Antiemetic regimen 1 containing granisetron 0, 04 mg/kg plus dexamethasone 0, 2 mg/kg were given in 45 chemotherapy cycles. In 31 cycles, an antiemetic cocktail containing midazolam 0, 04 mg/kg, diphenhyramine 2, 5 mg/-kg in addition to granisetron plus dexamethasone was given. Number of vomiting, severity of nausea, the use of rescue therapy and adverse events were assessed between day 1 and day 5.Results:Complete response for the acute phase was observed 38/45 (84, 4%) cycles in regimen 1 as compared with 28/31 (90, 3%) in regimen 2, antiemetic cocktail regimen (P > 0.05). Complete response for delayed emesis after 24 h of the beginning of chemotherapy was observed in 29/45 (64, 4 %) in regimen 1 and 16/31 (51, 6%) in regimen 2. Antiemetic cocktail was not superior to the granisetron plus dexamethasone combination in controlling emesis in acute and delayed phase. Furthermore, patients receiving antiemetic regimen 2 were noted significantly more side effects.Conclusion:Our data showed that antiemetic cocktail containing midazolam and diphenhydramine was not better in controlling acute and delayed emesis. A slightly more toxicity with additional drugs was also observed.