Composite intravenous lipid emulsion (ILE) containing soybean (30%), medium chain triglycerides (MCT) (30%), olive (25%) and fish (15%) oil (SMOFlipid®) is now widely used in the world for prematures, newborns and children on parenteral nutrition (PN). Long-term use in children on home-PN (HPN) is not documented. The aim was to assess the fatty acids (FA) profile of such HPN children. Population: 26 children with chronic intestinal failure (CIF) were assessed [SBS = 10, congenital enteropathy = 9, total aganglionosis = 4, CIPOS = 3] aged 6 months-16 years on home-PN for 12 months-16 years, highly dependent on PN (low plasma citrulline levels and high PN intake). All received SMOFlipid® as source of ILE for 12 - 38 months at the dose of 2.1 ± 0.39 g/kg/day, 6.7 ± 0.7 days/week. They were compared to 26 SBS children aged 7.8±3.9 years, weaned off PN for > 2 years. Methods: Sampling performed after ≥ 24h fat free PN and 6-8h after PN discontinuation. Red blood cell (RBC) fatty acids (FA) profiles were established by using gas-chromatography. Citrulline plasma levels, ratio non protein energy PN-intake(NPE)/resting energy expenditure (REE) - Schofield equation-, growth parameters in Z-score and total bilirubin were assessed.. FA profiles and Holman ratio (triene/tetraene) were compared to those obtained from the control group. Results: NSD: No significant difference. Conclusion: Long-term administration of an ILE rich in fish oil (15%) in highly PN dependent children (PN/REE:130±20 %) is well tolerated. Bilirubin plasma levels remained low and growth was normal. The RBC-FA profile, reflects the n-3/n-6 FA acid composition of this new fish oil rich ILE, without EFA deficiency as assessed by the Holman ratio. This “new” RBC-FA profile, followed on the long term, is not accompanied with any harmful clinical effect and can be considered as safe and probably beneficial for preventing IFALD.