When adequate nutrition cannot be provided by enteral route as a consequence of failure of intestinal functions, parenteral nutrition (PN) become the only way to maintain adequate nutrition; however, prolonged periods of PN can lead to severe complications. Furthermore, long hospital admissions for this form of nutrition can be detrimental for the child and the family. In the past 20 years, home parenteral nutrition (HPN) programs have been developed. The aim of our study was to retrospectively evaluate the kind and the frequency of complications in a HPN pediatric case series. We had 61 patients on HPN. Total duration of the program was 27,740 days (76 total years, mean 1.2 years per patient). We observed a total of 58 complications; mean 0.79 per patient per year with a prevalence of central venous catheter-related complications (mechanical, 52%; infective, 26%). We had a very low incidence of metabolic complications (3%) and a low incidence of PN-related hepatic complications (19%). None of the complications described was the cause of death. Half of our patients have been able to stop the program. We had a low incidence (0.20 per patient per year) of septic episodes, lower than we had in patients on hospital PN in the same period (0.38 per patient per year). We had to replace 20 catheters, 18 of them for mechanical problems. Our study shows that HPN still can be a valid alternative to small intestinal transplantation in patients affected by intestinal failure and that only patients with PN-related liver disease must be considered early candidates for combined liver-small bowel transplant.