To evaluate the effect of a regular oropharyngeal application of povidone-iodine on the prevalence of ventilator-associated pneumonia in patients with severe head trauma. Prospective randomized study. A surgical intensive care unit of a university hospital. Patients with severe head trauma (Glasgow Coma Score of < or =8) expected to need ventilation for > or =2 days were prospectively randomized into three groups: those receiving nasopharynx and oropharynx rinsing with 20 mL of a 10% povidone-iodine aqueous solution, reconstituted in a 60-mL solution with sterile water (povidone-iodine group); those receiving nasopharynx and oropharynx rinsing with 60 mL of saline solution (saline group); or those undergoing a standard regimen without any instillation but with aspiration of oropharyngeal secretions (control group). The prevalence of ventilator-associated pneumonia was compared among the three groups. A total of 98 patients were analyzed (povidone-iodine group, n = 36; saline group, n = 31; and control group, n = 31). A total of 28 cases of ventilator-associated pneumonia were diagnosed. There was a significant decrease in the rate of ventilator-associated pneumonia in the povidone-iodine group when compared with the saline and control groups (3 of 36 patients [8%] vs. 12 of 31 patients [39%] and 13 of 31 patients [42%], respectively; p = .003 and .001, respectively). The length of stay and mortality in the surgical intensive care unit were not statistically different between the three groups. The regular administration of povidone-iodine may be an effective strategy for decreasing the prevalence of ventilator-associated pneumonia in patients with severe head trauma.