Neonates with congenital cardiac disease are a special population. They are often critically ill, and need prolonged intravenous access. To date, no study has evaluated the efficacy and safety of peripherally inserted central venous catheters placed in this unique population. Our goal was to evaluate the use of such catheters in neonates with critical congenital cardiac disease, and to study features such as duration of use, reasons for removal of catheters, and complications. We inserted a total of 124 catheters in 115 neonates with critical congenital cardiac disease who were admitted to the Intensive Care Unit at Texas Children's Hospital from August 2002 to August 2004. The patients had a mean age of 10 days, and a mean weight of 3.1 kilograms. The peripherally inserted catheters were in place for a mean of 22.3 days. Therapy was completed in 76.6% patients at the time of removal of the catheter. The incidence of occlusion, dislodgement, and thrombus was 4.0%, 2.4%, and 1.6%, respectively. The infection rate was 3.6 per 1000 catheter-days, with a median onset on 37 days after placement. We conclude that central venous catheters, when inserted peripherally, provide reliable and safe access for prolonged intravenous therapy in neonates with critical congenital cardiac disease.