Children with intestinal failure (IF) require long‐term central venous access to provide life‐sustaining parenteral nutrition. Mechanical, thrombotic, and infectious complications are potentially life‐threatening and may necessitate central venous catheter (CVC) replacement. Repeated central line replacements may lead to a loss of vascular access sites and increases risk for intestinal transplantation. Children with IF face unique challenges for CVC safety given their young age, altered anatomy, and increased risk of thrombosis and infection. The following review addresses preventative, diagnostic, and treatment strategies for central line safety concerns specific to children with IF as well as recommendations for promoting catheter safety during activities, travel, and emergencies.