Abstract Purpose This phase III trial was designed to test trolamine emulsion compared with the usual supportive care for patients with head and neck cancer undergoing radiation therapy with concurrent chemotherapy. Patients and methods Patients with biopsy-proven head and neck squamous cell carcinoma (HNSCC) treated with radical radiotherapy and weekly concurrent cisplatin 40 mg/m2 at the South Egypt Cancer Institute (Assiut) were randomly assigned to one of the following groups: treatment group (prophylactic trolamine emulsion every 8 h, 4 h apart from the radiotherapy session) or control group (usual supportive care). The primary outcome was the reduction of grade III or higher skin toxicity, as per RTOG Acute Radiation Toxicity Criteria. Results From March 2008 to June 2009, 30 patients were entered onto the trial. The average age was 54.5 years. Patients were predominately male (83%) and most continued to use tobacco products (70%). The rate of skin-reaction was 100% in both groups. A mild radiation reaction (grades I and II) occurred as follows: 80% (12/15 cases) in the treatment group and 46.6% (7/15 cases) in the control group. A grade III skin reaction developed in 20% (3/15 cases) in the treatment group and 53.3% (8/15 cases) in the controls. There was a significant difference (P  0.01) between the two groups. Conclusion Our results confirm that trolamine emulsion significantly reduces the intensity of acute dermatitis following 3D-CRT with weekly cisplatin in HNSCC.