- Increased survival of extremely low birth weight infants depends on the use of indwelling catheters. These catheters expose the infant to the risk of thrombus formation and line infection. When intracardiac thromboses become infected, the entity is indistinguishable from infective endocarditis and exposes the infant to prolonged sepsis and risk of disseminated infected emboli. Despite prolonged antiinfective therapy and removal of the infected line, resolution of the sepsis and dissolution of the vegetations is frequently not achieved. We describe 2 cases of infective endocarditis in extremely low birth weight infants successfully treated with recombinant tissue plasminogen activator in addition to prolonged antiinfective therapy. Blood cultures became sterile and vegetations disappeared within days of commencing treatment, and there were no systemic complications. A literature search detailed in the article confirms the poor outcome associated with infectious endocarditis in preterm infants. Tissue plasminogen activator may play an important role when standard care has failed.