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To test the hypothesis that implementation of a marked reduction in intravenous fat will result in reversal of parenteral nutrition–associated liver disease (PNALD) in infants.Prospective study of intravenous fat emulsion reduction in parenteral nutrition to 1 g/kg/d 2 times per week in neonates diagnosed with PNALD. Primary outcome measure was total bilirubin levels compared with gestational age, birth weight, and diagnosis-matched historical controls receiving 3 g/kg/d of intravenous lipids.Intravenous fat emulsion reduction resulted in a significant decline in total bilirubin levels compared with controls. Comparison of growth in the 2 groups was similar. Mild essential fatty acid deficiency was detected in 8 of 31 infants and was reversed with additional days of lipid infusion. No significant adverse events were noted.An association between intravenous lipid emulsion administration and the development of PNALD seems probable. Use of intravenous fat emulsion reduction is a potential approach to reverse PNALD in young infants. Frequent monitoring of essential fatty acid deficiency is needed with the use of this regimen.