Total pancreatectomy and islet autotransplantation (TPIAT) for pancreatitis may induce risk for essential fatty acid deficiency (EFAD) due to exocrine pancreatic insufficiency and intestinal alterations. The prevalence of EFAD post-TPIAT is currently unknown. We abstracted essential fatty acid (EFA) profiles (n = 332 samples) for 197 TPIAT recipients (72% adult, 33% male). Statistical analyses determined the prevalence of, and associations with, EFAD post-operatively. EFAD was defined as a Triene-to-Tetraene ratio ≥ 0.05 if <18 years old, or ≥ 0.038 if ≥18 years old. Prevalence of EFAD was 33%, 49%, and 53.5% at 1, 2, and ≥ 3 years. At 1 year post-TPIAT, older age at transplant (p = 0.03), being an adult versus a child (p = 0.0024), and obstructive etiology (p = 0.0004) were significant predictors of EFAD. Only 6% of children had EFAD 1 year post-TPIAT vs. 46% of adults. ALA levels were lower with lower BMI at transplant (p = 0.011). EFAD was associated with the presence of other intestinal diseases (p < 0.0001). One-third of individuals had EFAD 1 year post-TPIAT, highlighting the need for systematic monitoring. Older age at transplant increased risk and adults were more affected than children. Other diagnoses affecting intestinal health may further increase risk for EFAD.