Nosocomial infective endocarditis (NIE) is a relatively uncommon but nevertheless a serious complication affecting critically ill hospitalized patients who are frequently exposed to life-saving invasive procedures. We report three cases of NIE in a tertiary-care hospital encountered during a period of two years. The first case developed in a 50% burn-injured patient; the second in a liver transplant recipient; and the third in a renal transplant recipient. All patients met indications for cardiac surgical intervention, however, the patient who had received a liver transplant (case 2) was considered a poor candidate and unfit for surgery; she subsequently died. The other two patients underwent open-heart surgery. The burns patient (case 1) survived; conversely, the renal transplant recipient (case 3) died postoperatively. We have reviewed the literature concerning NIE in critically ill patients and describe the epidemiology, microbiology and clinical features of this uncommon infection and comment on its diagnosis and management.