We sought to determine the impact of prenatal diagnosis on the perioperative outcome of newborns with hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA). All neonates with HLHS or TGA encountered at Children's Hospital, Boston, Massachusetts, from January 1988 to May 1996 were identified and outcomes documented. Birth characteristics, preoperative, operative, and postoperative variables of term newborns with a prenatal diagnosis of HLHS or TGA who underwent a Norwood operation (n = 27) or arterial switch operation (n = 14), respectively, were compared with newborns with a postnatal diagnosis of HLHS (n = 47) or TGA (n = 28) who had undergone surgery. Of 217 neonates with HLHS and 422 with TGA, 39 and 16, respectively, had a prenatal diagnosis. The preoperative mortality among neonates aggressively managed did not differ between the prenatal and postnatal diagnosis groups for either HLHS or TGA (p >0.05). Neonates with a prenatal diagnosis who underwent surgery had objective indicators of lower severity of illness preoperatively, including a higher lowest recorded pH (p = 0.03), lower maximum blood urea nitrogen (p = 0.002), and creatinine (p = 0.03) among newborns with HLHS, and a tendency toward higher minimum of partial pressure of arterial oxygen in the TGA group (p = 0.06). Prenatal diagnosis was not associated with an improved postoperative course or operative mortality (p <0.05) within a diagnostic group. Thus, a prenatal diagnosis improves the preoperative condition of neonates with HLHS and TGA, but may not significantly improve preoperative mortality or early postoperative outcome among neonates managed at a tertiary care center.