AbstractA recent case report by Shepard et al. (Teratology43:113–117, 1991) suggested that single ventricle may result from maternal cocaine ingestion by inducing coronary occlusion in the developing fetal heart. We used data from the Atlanta Birth Defects Case‐Control Study and the Metropolitan Atlanta Congenital Defects Program (MACDP) to investigate the role of maternal cocaine ingestion in the induction of single ventricles. We identified through the MACDP 58 case infants with a single ventricle, 27 who were study subjects in the Atlanta Birth Defects Case‐Control Study, and 31 who were not. We conducted a case‐control study with the 27 Atlanta Birth Defects Case Control Study infants, frequency‐matched to control infants by race, hospital of birth, and calendar quarter of birth. None of the 27 case infants were exposed to cocaine during early pregnancy, but 7 (0.43%) of the control infants were exposed during early pregnancy. Using MACDP data, we conducted an analysis of trends for prevalence of single ventricle in the metropolitan area. No upward trend in single ventricle was detected for 1968 through 1990. Our data suggest that even if maternal cocaine ingestion during pregnancy is a cause of single ventricle, most cases appear to be unrelated to this exposure. © 1992 Wiley