Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis (CF) and pancreatic insufficiency (PI). Efficacy of LYM-X-SORBTM (LXS), an easily absorbable lipid matrix that enhances fat absorption was evaluated in a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty acids (FA), and coefficient of fat absorption (CFA) outcomes. 110 subjects (age 10.4±3.0 y) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58; +1.14 mmol/L) and not with placebo (P=0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298; +175 nmol/mL, P≤0.046), with a 6% increase in CFA (P<0.01). LA increase was significant in LXS vs. placebo (445 vs. 42 nmol/mL, P= 0.038). Increased FA and LA predicted increased BMI Z scores. In summary, LXS treatment improved dietary fat absorption compared to placebo as indicated by plasma FA and LA and was associated with better growth status.