Objective:To determine whether additional therapy aimed at correcting low gastric intramucosal pH (pHi) improves outcome in conventionally resuscitated, critically ill patients.Design:Prospective, randomized, controlled study.Setting:General intensive care unit (ICU) of a university teaching hospital.Patients:A total of 210 adult patients, with a median Acute Physiology and Chronic Health Evaluation II score of 24 (range, 8-51).Interventions:All patients were resuscitated according to standard guidelines. After resuscitation, those patients in the intervention group with a pHi of <7.35 were treated with additional colloid and then dobutamine (5 μg/kg/min then 10 μg/kg/min) until 24 hrs after enrollment.Measurements and Main Results:There were no significant differences (p> .05) in ICU mortality (39.6% in the control group vs. 38.5% in the intervention group), hospital mortality (45.3% in the control group vs. 42.3% in the intervention group), and 30-day mortality (43.7% in the control group vs. 40.2 in the intervention group); survival curves; median modified maximal multiorgan dysfunction score (10 points in the control group vs. 13 points in the intervention group); median modified duration of ICU stay (12 days in the control group vs. 11.5 days in the intervention group); or median modified duration of hospital stay (60 days in the control group vs. 42 days in the intervention group). A subgroup analysis of those patients with gastric mucosal pH of ≥7.35 at admission revealed no difference in ICU mortality (10.3% in the control group vs. 14.8% in the intervention group), hospital mortality (13.8% in the control group vs. 29.6% in the intervention group), or 30-day mortality (10.3% in the control group vs. 26.9% in the intervention group).Conclusions:The routine use of treatment titrated against pHi in the management of critically ill patients cannot be supported. Failure to improve outcome may be caused by an inability to produce a clinically significant change in pHi or because pHi is simply a marker of disease rather than a factor in the pathogenesis of multiorgan failure.