Objective: To assess the effects of an antiseptic, non-alcohol based mouth-rinse containing chlorhexidine and cetylpyridinium chloride, in preventing the oral complications associated to radiation therapy in head-and-neck cancer patients. Study design: This was a parallel, double blind, prospective, randomized clinical trial. Cancer patients were randomly assigned to one of the two treatments (test mouth-rinse or a placebo). Three visits were scheduled (baseline, 14 and 28 days). Different outcome variables were evaluated: mucositis, plaque and gingival indices, stimulated saliva and salivary pH. Results: 70 patients were screened and 36 were included. The presence and the degree of mucositis significantly increased in both groups and no significant differences were detected between groups, although the median increase in the placebo group (1.81) at 2 weeks was higher than in the test group (1.20). Conclusions: Within the limitations of the small sample size, this study suggests that the use of the tested mouthrinse may lead to some improvements in clinical parameters in patients irradiated for head-and-neck cancer.