Background: Specific immunonutrients may reduce the incidence of postoperative complications and shorten recovery time. This randomized trial evaluated the clinical efficacy of a fish oil emulsion on outcome and immune function after gastrointestinal cancer surgery. Methods: A total of 206 patients with gastrointestinal or colonic cancer were randomized to receive isocaloric and isonitrogenous intravenous infusions of either soybean oil alone (1.2 g per kg bodyweight per day; control group, 103 analysed) or soybean plus fish oil emulsion (1.0 and 0.2 g per kg per day respectively; treatment group, 100 analysed) over 20-24 h daily for 7 days after surgery. Results: Baseline data were comparable in the two groups. There were fewer infectious complications (four versus 12 on day 8; P = 0.066), systemic inflammatory response syndrome (SIRS) was significantly less common (four versus 13; P = 0.039) and hospital stay was significantly shorter (mean(s.d.) 15(5) versus 17(8) days; P = 0.041) in the treatment group. Total postoperative medical costs were comparable in the two groups (mean(s.d.) US $1269(254) and 1302(324) in treatment and control groups respectively; P = 0.424). The median (interquartile range) difference in CD4/CD8 between days 1 and 8 after surgery was +0.30 (0.06 to 0.79) in patients receiving fish oil and +0.20 (-0.19 to 0.55) in controls (P = 0.021). No severe adverse events occurred in either group. Conclusion: Fish oil emulsion-supplemented parenteral nutrition significantly reduced SIRS and length of hospital stay. These clinical benefits may be related to normalization of cellular immune functions and modulation of the inflammatory response. Registration number: NCT00292279 (http://www.clinicaltrials.gov).