OBJECTIVE: To conduct a meta-analysis of 11 randomized controlled trials comparing enteral nutritional support supplemented with key nutrients versus standard enteral nutritional support to determine effects on morbidity and mortality rates and hospital stay. BACKGROUND DATA: Recent studies have shown that malnutrition occurs in up to 30% of patients undergoing gastrointestinal surgery, resulting in an increased risk of postoperative complications and death. With the realization that key nutrients can modulate inflammatory, metabolic, and immune processes, enteral nutritional regimens (supplemented with large amounts of key nutrients) have been developed for clinical use. METHODS: Eleven prospective, randomized controlled trials evaluating 1009 patients treated with combinations of key nutrients (Impact, Immun-Aid) were evaluated. Outcome measures examined were the incidences of pneumonia, infectious complications, and death, and length of hospital stay. Meta-analyses were undertaken to obtain the odds ratio and 95% confidence interval for incidences of infectious complications, pneumonia, and death, and the weighted mean difference and 95% confidence interval for length of hospital stay. RESULTS: The provision of nutritional support supplemented with key nutrients to patients with critical illness resulted in a decrease in infectious complications when compared with patients receiving standard nutritional support and a significant reduction in overall hospital stay. Similar results were documented in patients with gastrointestinal cancer. However, there were no differences between patient groups for either pneumonia or death. CONCLUSIONS: This meta-analysis has demonstrated that nutritional support supplemented with key nutrients results in a significant reduction in the risk of developing infectious complications and reduces the overall hospital stay in patients with critical illness and in patients with gastrointestinal cancer. However, there is no effect on death. These data have important implications for the management of such patients.