Background: This study sought to compare 2 strategies for the administration of enteral feeding to mechanically ventilated medical patients. Methods: The prospective, controlled, clinical trial was carried out in a medical intensive care unit (19 beds) in a university-affiliated, urban teaching hospital. Between May 1999 and December 2000, 150 patients were enrolled. Patients were scheduled to receive their estimated total daily enteral nutritional requirements on either day 1 (early-feeding group) or day 5 (late-feeding group) of mechanical ventilation. Patients in the late-feeding group were also scheduled to receive 20% of their estimated daily enteral nutritional requirements during the first 4 days of mechanical ventilation. Results: Seventy-five (50%) consecutive eligible patients were entered into the early-feeding group and 75 (50%) patients were enrolled in the late-feeding group. During the 5 five days of mechanical ventilation, the total intake of calories (2370 ± 2000 kcal versus 629 ± 575 kcal; p < .001) and protein (93.6 ± 77.2 g versus 26.7 ± 26.6 g; p < .001) were statistically greater for patients in the early-feeding group. Patients in the early-feeding group had statistically greater incidences of ventilator-associated pneumonia (49.3% versus 30.7%; p = .020) and diarrhea associated with Clostridium difficile infection (13.3% versus 4.0%; p = .042). The early-feeding group also had statistically longer intensive care unit (13.6 ± 14.2 days versus 9.8 ± 7.4 days; p = .043) and hospital lengths of stay (22.9 ± 19.7 days versus 16.7 ± 12.5 days; p = .023) compared with patients in the late-feeding group. No statistical difference in hospital mortality was observed between patients in the early-feeding and late-feeding groups (20.0% versus 26.7%; p = .334). Conclusions: The administration of more aggressive early enteral nutrition to mechanically ventilated medical patients is associated with greater infectious complications and prolonged lengths of stay in the hospital. Clinicians must balance the potential for complications resulting from early enteral feeding with the expected benefits of such therapy.