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To evaluate whether selective digestive decontamination (SDD) reduces mortality from any cause, and the incidence of pneumonia among patients with severe burns.SDD is a prophylactic strategy to reduce infectious morbidity and mortality in critically ill patients. Two meta-analyses and a recent randomized controlled trial demonstrated a mortality reduction varying between 20% and 40%. But this technique has never been properly evaluated in severely burned patients.The design of this single-center trial was randomized, double blind, placebo controlled. Patients with burns ≥20% of total body surface and/or suspected inhalation injury were enrolled and assigned to receive SDD or placebo for the total duration of treatment in the burn intensive care unit (ICU).One hundred seventeen patients were randomized and 107 were analyzed (53 in the SDD group and 54 in the placebo group). The ICU mortality was 27.8% in the placebo group and 9.4% in the SDD group in the burn ICU. Treatment with SDD was associated with a significant reduction in mortality both in the burn ICU (risk ratio 0.25; 95% CI 0.08 to 0.76) and in the hospital (risk ratio 0.28; 95% CI 0.10 to 0.80), following adjustment for predicted mortality. The incidence of pneumonia was significantly higher in the placebo group: 30.8 and 17.0 pneumonias per 1000 ventilation days (P = 0.03) in placebo and SDD group, respectively.Treatment with SDD reduces mortality and pneumonia incidence in patients with severe burns.