Introduction: Supplementation of clinical nutrition with fish oil, rich in n-3 fatty acids, exerts immune-modulating and organ protective effects, even after short term infusion. We evaluated the impact of supplementation of total parenteral nutrition (TPN) with a 10% fish-oil (FO) emulsion (Omegaven-Fresenius) on the clinical course. Primary study end point was occurrence of infections, secondary endpoint was length of hospital stay (LOS). Materials and methods: 661 Patients from 82 German hospitals who received TPN for at least 3 days were enrolled in this prospective multicenter trial. Amongst the patients were 233 (35.2%) after major abdominal surgery, 268 (40.5%) with peritonitis, 33 (5%) with pancreatitis, 45 (6.8%) after multiple trauma,13 (2%) with severe head injury and 9 (1.3%) had non abdominal sepsis. TPN was supplemented with 0.11 g/kg/d of FO. Exclusion criteria were lipid or coagulation disorders, severe diabetes mellitus and circulatory shock. Results: The patients enrolled in this survey were 62.8 +/- 16.4 years old, with a body mass index of 25.1 +/- 4.2. LOS was 29.1 +/- 18.7 days (12.5 +/- 14.8 ICU). TPN including FO was administered for 8.7 +/- 7.5 days and was well tolerated. The infection rate was significantly lower as expected. Patients who received at least 5% of the daily calorie intake as FO had lower demand of antibiotics within the observation period. While no changes in LOS were detected in the overall study population, postoperative patients were judged to have a shorter LOS. Likewise, complications occurred rarer under fish oil supplementation as expected. Moreover, evaluation of the patients clinical course was found more advantageous (p < 0.001). The two mean factors contributing to the LOS in a multifactor-regression model were amount of n-6 fatty acids (+ 1.6 d/100 g) and the delay of nutrition (+ 1.42 d/day of delay). Conclusion: Fish oil supplementation of TPN is well tolerated and has favourable effects on the recovery of distinct patient populations,