Objective:To evaluate the effect of acidified enteral feeds on gastric colonization in critically ill patients compared with a standard feeding formula.Design:Randomized, double-blind, multicenter trial.Setting:Eight mixed intensive care units at tertiary care hospitalsPatients:We recruited mechanically ventilated critically ill patients expected to remain ventilated for >48 hrs. We excluded patients with gastrointestinal bleeding, acidemia, and renal failure requiring dialysis. We enrolled 120 patients; 38% were female, age (mean ± SD) was 57.6 ± 19.3 yrs, and Acute Physiology and Chronic Health Evaluation II score (mean ± SD) was 21.6 ± 7.6.Interventions:Vital High Nitrogen (Abbott Laboratories, Ross Products Division, Columbus, OH) was used as the standard feeding formula for the control group (pH = 6.5). Hydrochloric acid was added to Vital High Nitrogen to achieve a pH of 3.5 in the experimental group.Measurements and Main Results:The main outcome measure was gastric colonization. Secondary outcomes included gastric pH, pneumonia, and mortality. The mean gastric pH in patients receiving acid feeds was lower (pH = 3.3) compared with controls (pH = 4.6;p< .05). One patient (2%) on acid feeds was colonized in the stomach with pathogenic bacteria, compared with 20 patients (43%) in the control group (p< .001). There was no difference in the incidence of pneumonia (6.1% in the acid feeds group vs. 15% in the control group;p= .19). Overall, there were 15 deaths in the acid feeds group and seven in the control group (p= .10); four patients in the acid feeds group and three in the control group died during the study period (pnot significant).Conclusions:Acidified enteral feeds preserve gastric acidity and substantially reduce gastric colonization in critically ill patients. Larger studies are needed to examine its effect on ventilator-associated pneumonia and mortality.