Children with intestinal failure often require long-term central venous access for parenteral nutrition. Line-related complications often include liver dysfunction, sepsis, and loss of venous access. Osteomyelitis is a rare complication that has been reported in adults with intestinal failure. There has been little focus, however, on the development of osteomyelitis in the pediatric population. In this study we present 2 case studies of patients with intestinal failure requiring parenteral nutrition who subsequently developed acute osteomyelitis.