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This prospective randomized 2-period crossover study aimed at comparing the efficacy of 2 oral care protocols differing in the type of mouthwashes: chlorhexidine versus benzydamine in alleviating oral mucositis symptoms for children undergoing chemotherapy. Forty subjects were randomly allocated to receive either chlorhexidine first then benzydamine protocols or benzydamine first then chlorhexidine protocols. Each protocol was started on the first day of chemotherapy and continued for 21 days. Subjects were evaluated in intervals of 3 to 4 days using the World Health Organization (WHO) grading for mucositis and 10-cm visual analogue scale for oral symptoms evaluations. Among 34 evaluable subjects, 26% and 48% of them using chlorhexidine and benzydamine had WHO grade II mucositis, respectively (P < .05). The results revealed a significant difference in mean area under the curve (AUC) of mouth pain (1.35 ± 2.26 versus 3.09 ± 3.21) (P = .05), and a trend of a lessening of mean AUC of difficulty in eating/chewing (2.49 ± 3.74 versus 2.71 ± 4.1) (P = .82) and swallowing (1.34 ± 3.31 versus 1.91 ± 4.03) (P = .53) for subjects receiving chlorhexidine compared to those receiving benzydamine. In conclusion, chlorhexidine may be helpful in palliating mucositis symptoms for children in chemotherapy. The beneficial effect, however, is small and needs to be confirmed in a larger trial.