Nutritional support is part of the standard of care for the critically ill adult patient. In the average patient in the intensive care unit who has no contraindications to enteral nutrition (EN) or parenteral nutrition (PN), the choice of route for nutritional support may be influenced by several factors. Because EN and PN are associated with risks and benefits, we systematically reviewed and critically appraised the literature to compare EN with PN the critically ill patient. We searched computerized bibliographic databases, personal files, and relevant reference lists to identify potentially eligible studies. Only randomized clinical trials that compared EN with PN in critically ill patients with respect to clinically important outcomes were included in this review. In an independent fashion, relevant data on the methodology and outcomes of primary studies were abstracted in duplicate. The studies were subsequently aggregated statistically. There were 13 studies that met the inclusion criteria and, hence, were included in our meta-analysis. The use of EN as opposed to PN was associated with a significant decrease in infectious complications (relative risk = 0.64, 95% confidence interval = 0.47 to 0.87, P = 0.004) but not with any difference in mortality rate (relative risk = 1.08, 95% confidence interval = 0.70 to 1.65, P = 0.7). There was no difference in the number of days on a ventilator or length of stay in the hospital between groups receiving EN or PN (Standardized Mean Difference [SMD] = 0.07, 95% confidence interval = -0.2 to 0.33, P = 0.6). PN was associated with a higher incidence of hyperglycemia. Data that compared days on a ventilator and the development of diarrhea in patients who received EN versus PN were inconclusive. In the EN and PN groups, complications with enteral and parenteral access were seen. Four studies documented cost savings with EN as opposed to PN. The use of EN as opposed to PN results in an important decrease in the incidence of infectious complications in the critically ill and may be less costly. EN should be the first choice for nutritional support in the critically ill.