OBJECTIVE To determine the incidence and distribution of neonatal sepsis in premature newborns with congenital heart disease (CHD) according to gestational and postnatal age, time of onset, and type and frequency of causing agents, and compare it with premature newborns without CHD. DESIGN, SETTING, PATIENTS A clinical investigation on 80 premature newborns admitted to neonatal intensive care unit (NICU) of Pediatric Clinic University Medical Center Sarajevo, Bosnia and Herzegovina, between October 23, 2007 and March 18, 2009. We analyzed the incidence and distribution of neonatal sepsis in premature newborns with CHD according to gestational and postnatal age, time of onset, and type and frequency of causing agents, and compared it with premature NICU patients without CHD. RESULTS Of the 80 premature newborns included in our study, 14 had CHD with patent ductus arteriosus as the most common type of anomaly. Culture-proven sepsis was diagnosed in 28.57% premature newborns with CHD and 12.12% premature newborns without CHD. The three most common causing agents were Staphylococcus aureus, Klebsiella species, and Serratia species. CONCLUSION Premature newborns with CHD have a higher risk of acquiring sepsis during hospitalization in NICU, probably because of longer duration of hospitalization and need for invasive procedures such as mechanical ventilation, central venous catheters, and parenteral nutrition.