OBJECTIVE To assess the incidence and spectrum of complications associated with central venous catheter (CVC) placement in the critically ill infant. DESIGN A prospective study of all babies hospitalized in a neonatal intensive care unit (NICU) from January 1989 to December 1989. Potential risk factors associated with infection were evaluated by a case-control comparison. SETTING Conducted at a university-affiliated, tertiary care community hospital. PATIENTS Neonates requiring intensive care and a central venous catheter. Controls consisted of noninfected babies. RESULTS Of 263 critically ill neonates, only 13 (4.9%) required a CVC insertion. Seventeen CVCs were placed in these 13 neonates for a total duration of 600 days (median, 32 days/cannula). Fifteen (88%) of these cannulas had one or more complications during its catheter life including dislodgement or leakage (53%), occlusion or thrombosis (47%), infections (29%), or minor bleeding (12%). Five babies (29%) developed 6 episodes of bloodstream infection including 3 sporadic cases due to Staphylococcus epidermidis and a cluster of fungemia due to Malassezia furfur associated with lipid emulsion therapy. Infants with a CVC-associated infection were a younger gestational age (24 weeks versus 32 weeks, p = .04) and weighed less at birth (580 g versus 1285 g, p = .02). The overall rate of bloodstream infection was one episode per 100 days of catheter use. CONCLUSIONS CVCs may be lifesaving to a critically ill neonate, but complications occur frequently. Use must be restricted to infants in whom alternate delivery routes of intravenous therapy or support are otherwise unavailable.