Home parenteral nutrition (HPN) is a life-sustaining therapy for children and adults suffering with severe digestive diseases, yet complications are commonplace, and predischarge trainings are variable. High-fidelity simulation training provides participants with an immersive experience using realistic equipment, supplies, and scenarios. Simulation training is rapidly becoming a potential gold standard for healthcare but is currently underutilized for families and caregivers. We prospectively collected data on pediatric patients managed at a single HPN program from September 1, 2016, to September 30, 2018. Participants in a pilot simulation-based training program (orientation, high-fidelity mannequin, realistic homelike space, standardized clinical scenarios, and structured debriefing) were compared with historical controls. We excluded patients with short-term HPN use and strictly palliative goals of care. Nineteen (90%) families participated in the pilot initiative with a median (interquartile range) age of 0.9 (3.7) years and diagnosis of short-bowel syndrome in 14 (74%). During teaching scenarios, learning gaps were identified for aseptic needleless changes (53%), HPN equipment setup (84%) with specific difficulty adding multivitamin (32%), and dressing changes (63%). Thirty-day readmission rates in simulation-based training group vs historical cases were 42% vs 63% (P = not significant). There was no difference in length of stay between groups. All (100%) simulation-based training group participants would recommend this learning experience to others. HPN discharge training is a novel use for high-fidelity simulation to address family/caregiver satisfaction and to identify learning gaps. Further studies are needed to refine predischarge training materials and examine the impact on postdischarge outcomes. © 2019 American Society for Parenteral and Enteral Nutrition.