Introduction: Significant malnutrition exists in a high percentage of patients with head and neck cancer. Malnutrition is associated with defects in immune function that may impair the host response to malignancy. Malnutrition and immunosupression make patients highly susceptible to postoperative infections and complications. Objectives: Compare two immunoenhanced enteral nutritions with a control diet, and evaluate the effect in postoperative infections, length of stay and inflammatory markers. Patients: A population of 44 patients with oral and laryngeal cancer was enrolled in a randomized trial. At surgery, patients were randomly allocated to three groups: (group I); patients receiving an arginine-enhanced formula (group II); patients receiving a standard polymeric formula, and (group III) patients receiving an arginine, RNA and omega-3 fatty acids enhanced formula, in an isonitrogenous way. Results: The duration of enteral nutrition in the three groups was similar with an average duration of 14,5 ± 8 days. The length of postoperative stay was similar, with an average of 19,8 ± 8,5 days. Wound infections and general infections were more frequent in the control group. Fistula rates were not improved in the enhanced diet groups. No significant intergroup differences in the trend of the two plasma proteins (albumin, transferrin), lymphocytes, weight, IL-6, CPR and TNFα were detected. The control group showed the highest levels of TNFα at the fourteenth postoperative day. Gastrointestinal tolerance and diarrhoea rate were similar in all the patients. Conclusions: Immunoenhanced enteral nutrition formulas improved the infection rate in the postoperative of head and neck cancer patients. In the fistula rates, we observed that technical problems and nutritional status might have played an equally important role, and therefore the positive effect of immunonutrition in this parameter might have been overestimated.