OBJECTIVE: We investigated the prenatal prevalence of congenital heart defects (CHDs) among in vitro fertilization (IVF) pregnancies at a referral program in the United States. METHODS: Study patients were referred for fetal echocardiography between April 1, 2006, and May 1, 2009, due to IVF. An IVF pregnancy was defined as a patient who conceived with IVF with or without intracytoplasmic sperm injection. Congenital heart defect odds relative to historical data were calculated by standard methods. P < .05 was considered statistically significant. RESULTS: During the study period, we performed fetal echocardiography on 749 consecutive IVF pregnancies. Overall, the frequency of CHDs was 1.1% (95% confidence interval, 0.3%-1.8%) per pregnancy. Compared to earlier historical population data, IVF pregnancies had a significantly higher risk of CHDs (odds ratios, 7.3 [3.6-14.7] and 2.9 [1.4-5.9], respectively). However, compared to more contemporary population data, there was no difference in the CHD risk between IVF gestations and naturally conceived pregnancies. Further analysis indicated that IVF twin pregnancies were as much as 12.5 (4.6-33.5) times as likely to have CHDs compared to a general population. CONCLUSIONS: In this study population, the frequency of CHDs in IVF pregnancies was higher than early historical population data; however, it was similar to that of a more contemporary general population. Further analysis showed that this increase was mainly driven by IVF twin gestations. Previous reports of increased CHD risk in pregnancies conceived via IVF may have been due, in part, to an increased frequency of higher-order pregnancies seen among these patients.