OBJECTIVE To test the influence of continuously administered enteral feeding on gastric pH and gastric colonization in patients receiving or not receiving topical antimicrobial prophylaxis of the oropharynx and stomach, including sucralfate as stress ulcer prophylaxis. METHODS Prospective, open trial. METHODS Two university hospital general intensive care units (ICUs). METHODS Patients (n = 95) with an ICU stay for at least 5 days. METHODS Thirty-one patients received antimicrobial agents into the stomach and oropharynx in combination with sucralfate (1 g/6 hrs) as stress ulcer prophylaxis. Sixty-four other patients did not receive antimicrobial prophylaxis or sucralfate, but instead received gastric pH-increasing stress ulcer prophylactic agents, if indicated. Gastric colonization and gastric pH were measured on admission and subsequently at least two times a week. Forty-eight patients (14 receiving and 34 not receiving antimicrobial prophylaxis) received enteral feeding. RESULTS Both enteral feeding and gastric pH-increasing stress ulcer prophylaxis independently increased gastric pH: the risks for a gastric pH of > 3.5 were, respectively, 4.54 and 2.04 (odds ratios). Enteral feeding also increased the risk for gastric colonization by potentially pathogenic microorganisms (odds ratio = 4.52). Patients receiving both topical antimicrobial prophylaxis and sucralfate remained free of gastric colonization for a longer period than those patients receiving gastric pH-increasing stress ulcer prophylaxis. In these two groups, patients without enteral feeding remained free of gastric colonization for a longer period than those patients receiving enteral feeding. CONCLUSIONS Topical antimicrobial prophylaxis, including sucralfate, successfully prevented gastric colonization with potentially pathogenic microorganisms and was correlated with lower gastric pH values. However, the efficacy was markedly decreased when continuous enteral feeding was administered simultaneously.