Objective: To evaluate the effect of a method of Selective Decontamination of the Digestive Tract (SDD) on colonization, nosocomial infection (NI), bacterial resistance, mortality and economic costs. Design: Randomized, double blind, placebo controlled study. Setting: Polyvalent intensive care unit (ICU) of a tertiary care hospital with 27 beds. Patients: 101 patients with > 3 days of mechanical ventilation and > 5 days of stay, without infection at the start of the study. 47 belonged to the Treated Group (TG) and 54 to the Placebo Group (PG). Interventions: The TG was given Cefotaxime iv. (6 g/day) for the first four days and an association of Polymyxin E, Tobramycin and Amphothericin B at the oropharyngeal and gastrointestinal level throughout the whole stay. Results: In the TG, colonization by gram-negative agents at oropharyngeal, tracheal and gastrointestinal level fell significantly. There was a significant drop in the overall, respiratory and urinary NI (26% vs 63%, p < 0.001; 15% vs 46%, p<0.001; 9% vs 31%, p<0.01). The overall mortality and NI related mortality was less in the TG (21% vs 44%, p<0.05; 20% vs 20%, p<0.01). The economic costs, mechanical ventilation time and length of stay were similar. The percentage of bacterial isolations resistant to Cefotaxime and Tobramycin was greater in the TG (38% vs 15% and 38% vs 9%, p<0.001). Conclusions: colonization by gram-negative bacilli, NI and the mortality related to it can be modified by SDD. Continuous bacteriological surveillance is necessary.