Hypertriglyceridemia [Triglycerides (TG) >250 mg/dl] resulting from intravenous lipid infusions may adversely affect oxygenation. In animal studies, DEX increases de novo fatty acid synthesis, and induces HTG and hepatic lipoprotein production. Its independent role in causing HTG in neonates has not been determined. We hypothesized that therapeutic DEX is associated with HTG in neonates. We conducted a retrospective case-control study of infants with birth weight <1250 gm admitted to our NICU from 1993-1995. We identified 35 infants who developed HTG while receiving intralipid infusion between 1 week and 2 months of age. 8 cases met exclusion criteria [culture proven concurrent sepsis (5); concurrent major surgery (1); abnormal thyroid function (1);>4 gm/kg lipid intake (1)]. The remaining 27 cases were matched with randomly selected controls by post conceptional age, intralipid intake and aminophylline usage, but having normal TG levels. In both groups peak TG levels were evaluated. The odds ratio for DEX usage was estimated using standard methods for analyzing matched pair data. The maximum likelihood estimate for the odds ratio of developing HTG with DEX therapy was 17.0 with an “exact” 95% confidence interval of (2.66, 710.47), p<0.0001. We conclude that infants treated with DEX are at significantly higher risk of developing HTG than similar infants not treated with DEX. TG levels should be routinely checked in infants receiving DEX.