OBJECTIVE: To measure gastric emptying in critically ill patients using an acetaminophen absorption model and determine which variables are associated with impaired gastric emptying. DESIGN: A prospective, cohort study. SETTING: A medical/surgical ICU at a tertiary care hospital: Hamilton General Hospital, Hamilton, Ontario. PATIENTS AND PARTICIPANTS: We recruited 72 mechanically ventilated patients expected to remain in the ICU for more than 48 h. Our results were compared to those in healthy volunteers. INTERVENTION: Within 48 h of admission to the ICU, 1.6 g acetaminophen suspension were administered via a nasogastric tube into the stomach. Blood samples were drawn a t = 0, 30, 60, 90, and 120 min for measurement of plasma acetaminophen levels determined by the enzymatic degradation method. MEASUREMENTS AND RESULTS: Maximal concentration of acetaminophen was 94.1 (75.3) mumol/l compared to 208.4 (33.1) mumol/l in a control population (p < 0.0001). The time to reach the maximal concentration was 105 min (60-180) compared to 30 min (15-90) in controls (p < 0.0001). The area under the time-acetaminophen concentration curve t = 120 was 9301 (7343) mumol/min per l compared to 11644 (1336) mumol/min per l in the controls (p = 0.28). The variables associated with delayed gastric emptying were age, sex and use of opioids for analgesia and sedation. CONCLUSIONS: Gastric emptying is delayed in critically ill patients. The important consequences of this phenomenon include intolerance to enteral nutrition and gastric colonization. Strategies to minimize the use of narcotics may improve gastric emptying. Studies to examine the effect of gastrointestinal prokinetic agents on gastric emptying are needed.