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To determine whether medical intensive care unit (ICU) patients receiving nasoduodenal (ND) feedings achieve optimal nutritional support and better clinical outcomes compared with patients receiving nasogastric (NG) feedings.A prospective, randomized, clinical study.Medical ICU of a university-affiliated tertiary medical center.One hundred twenty-one medical ICU patients required enteral feeding.Patients were randomized to receive enteral feeding. One group received ND feedings and the other group received NG feedings. All patients followed the same protocol.The primary outcome of optimal nutritional support was assessed by measurement of time to goal tube feed rate and daily calorie and protein intake. Secondary clinical outcomes included number of ICU, hospital and ventilator days, number of the days in the study, blood–glucose levels, incidence of vomiting, diarrhea, gastrointestinal bleeding, tube replaced, tube clogged, fever, bacteremia, and ventilator-associated pneumonia (VAP), and mortality rate. Results showed that the ND group had a higher average daily calorie and protein intake compared with NG group and achieved nutritional goals earlier. In terms of clinical outcomes, patients in the ND group had a lower rate of vomiting and VAP. The other clinical outcomes such as number of ICU days, hospital days, ventilator days, blood–glucose level, tube replaced or clogged, diarrhea, gastrointestinal bleeding, fever, bacteremia, and mortality rate were not significantly different between two groups.Patients who received ND feedings achieved nutritional goals earlier than those who received NG feeding. ND feeding group also has a lower rate of vomiting and VAP in the medical ICU setting.