The pathophysiology of NEC is incompletely understood and so the search for causative factors continues. It has been shown that indomethacin produces significant reduction in mesenteric blood flow(1,2). We hypothesized that the risk of NEC would be increased in very low birth weight (VLBW) infants receiving indomethacin. With the advocation of prevention of intraventricular hemorrhage with prophylactic indomethacin(3,4), we conducted a case control study to investigate the association of NEC and use of indomethacin for closure of PDA in VLBW infants. There were 187 such infants admitted to the Health Sciences Centre Neonatal Intensive Care Unit between January 1993 and December 1994. Of these, 29 developed NEC compared to 158 who did not. The infants who developed NEC were of lower gestational age mean±SE (27.1±0.3 vs 28.8±0.2 p£0.001); birth weight (879±37 vs 1111±22 p£0.0000); and more developed PDA (53% vs 32% p£0.000). Infants who received indomethacin were over represented in the NEC group (29% vs 11.5% p£0.013). There were no differences in inotropic support; surfactant use; prenatal steroids; tocolytics (indomethacin); and the highest mean airway pressure. Indomethacin treatment of PDA is strongly associated with higher risk of developing NEC. This could be a cause-effect association or an indirect association due to birth weight and gestational age differences.