Oral mucositis is a common morbidity induced by radiation therapy and chemo-radiotherapy for head and neck malignancies. This often results in treatment delays, premature treatment cessation and increased cost. New treatments of oral mucositis are emerging but effective remedies remain limited. Between February 2007 and May 2008, 21 patients with head and neck malignancies were treated with a supersaturated calcium phosphate oral rinse (Caphosol) that was performed for 4-10 times daily, each consisting of two one-minute rinses. There were 21 matched patients who received supportive care without the oral rinse. All patients in the two groups were treated with intensity modulated radiation therapy (IMRT) for average prescription doses of 66 Gy in 33 fractions. The effects of this rinse vs. supportive care on mucositis, PEG tube requirements, hospitalization, xerostomia, analgesic requirements and weight was respectively evaluated. We have observed statistically significant decreases in the incidence of radiation induced oral mucositis (p=0.0002) with WHO grade 3 (38% vs. 52%) and 4 mucositis (0% vs. 19%), need for PEG tube placement (33% vs. 57%) and hospitalization (0% vs 19%). There was also a favorable impact on the incidence of grade 3 (29% vs. 43%) xerostomia in the treated patients but it was statistically insignificant (p=0.58). Incremental costs related to treatment of oral mucositis were reduced considerably. Our data suggest that use of a supersaturated calcium phosphate oral rinse is an effective treatment for mucositis in patients undergoing IMRT. It may also be helpful in the reduction of hospitalization and PEG tube requirements.