This pilot study was designed to compare the efficacy of 0.2% wt/vol chlorhexidine gluconate and 0.15% wt/vol benzydamine hydrochloride oral rinses in alleviating irradiation oropharyngeal mucositis for patients with head and neck cancer. This was a prospective, randomized, and double-blinded study. Fourteen subjects were stratified based on nasopharyngeal cancer and non-nasopharyngeal head and neck cancer, and were randomly assigned to receive oral care protocol either containing with chlorhexidine (n = 7) or benzydamine (n = 7) from the first day to 2 weeks after the completion of radiotherapy. Subjects were evaluated twice weekly through days 1 to 64 using the World Health Organization mucositis scale and the 10 cm visual analogue scale for mouth pain and dysphagia. In the chlorhexidine arm, 4 subjects (57%) had grade 2, and 3 subjects (43%) had grade 3 mucositis. In the benzydamine arm, 5 subjects (71%) had grade 2, and 2 subjects (29%) had grade 3 mucositis (P > .05). The mean area-under-the-curve values of mucositis were 26.5 +/- 13.6 (median 26) and 24.1 +/- 6.1 (median 22) in the chlorhexidine group and benzydamine group, respectively (P > .05). The mean area-under-the-curve values of pain and dysphagia were 70.8 +/- 33 (median 88.5) and 71.5 +/- 39 (median 101), and 62.1 +/- 17.2 (median 72) and 66 +/- 22.3 (median 57.5) in the chlorhexidine and benzydamine groups, respectively (P > .05). A trend has emerged of a lessening of severity of mucositis, pain, and dysphagia for patients with head and neck cancer receiving benzydamine oral rinse. The beneficial effects, however, need to be confirmed in a larger trial.