The most severe complication of necrotizing enterocolitis (NEC) is bowel perforation. Identification of neonates at high risk for perforation and optimization of radiologic imaging to identify bowel perforation are necessary to reduce the high mortality rate associated with this catastrophic event. One hundred and fifty-five cases of NEC were seen at our institution during a 5.5-year period. Nineteen (12%) progressed to perforation. A review of surgical findings, autopsy results and radiographs from these patients shows only 63% had radiographic evidence of free air in the peritoneal cavity at the time of perforation. Twenty-one percent had radiographic evidence of ascites but no pneumoperitoneum, and 16% had neither free air nor ascites. Thus purely radiographic criteria for bowel perforation in NEC are imprecise, and paracentesis is mandatory in NEC patients with ascites or clinical findings indicative of peritonitis. Timing of radiographic studies and site of bowel involvement are also important. Seventy-nine percent of perforations occurred by 30 h from confirmation of diagnosis (by clinical or radiographic criteria). Surgery or autopsy revealed involvement of the ileo-cecal region in 89% of cases with the actual site of perforation occurring in this area in 58% of patients.