Objective: To evaluate the incidence of congenital malformations among offspring of mothers who conceived with clomiphene citrate(CC) or with letrozole treatment for infertility. Design: Retrospective study. Setting: 5 fertility centers in Canada. Patients: 911 newborns from women who conceived following CC or letrozole treatment. Interventions: Examination of medical files of both mother and newborn, and cross-checked with the parents by telephone calls. Main Outcome Measures: Identified major and minor congenital malformations, birth weight, age of the mother, and type of treatment that led to the conception. Results: Overall, congenital malformations and chromosomal abnormalities were found in 14 of 514 newborns in the letrozole group(2.4%) and in 19 of 397 newborns in the CC group(4.8%). The major malformation rate in the letrozole group was 1.2%(6/514) and in the CC group was 3.0%(12/397). One newborn in the letrozole group was found to have a ventricular septal defect(0.2%)-compared to 4 newborns in the CC group(1.0%). In addition, the rate of all congenital cardiac anomalies was significantly higher(P: 0.02) in the CC group(1.8%) compared to the letrozole group(0.2%). Conclusion: There was no difference in the overall rates of major and minor congenital malformations among newborns from mothers who conceived after letrozole or CC treatments. However, it appears that congenital cardiac anomaly is less frequent in the letrozole group. The concern that letrozole use for ovulation induction could be teratogenic is unfounded based on our data. Objective: To evaluate the incidence of congenital malformations among offspring of mothers who conceived with clomiphene citrate (CC) or with letrozole treatment for infertility. Design: Retrospective study. Settings: 5 fertility centers in Canada. Patients: 911 newborns from women who conceived following CC or letrozole treatment. Interventions: Examination of medical files of both mother and newborn, and cross-checked with the parents by telephone calls. Main Outcome Measures: Identified major and minor congenital malformations, birth weight, age of the mother, and type of treatment that led to the conception. Results: Overall, congenital malformations and chromosomal abnormalities were found in 14 of 514 newborns in the letrozole group (2.4%) and in 19 of 397 newborns in the CC group (4.8%). The major malformation rate in the letrozole group was 1.2% (6/514) and in the CC group was 3.0% (12/397). One newborn in the letrozole group was found to have a ventricular septal defect (0.2%) - compa The addition of the rate of all congenital cardiac anomalies was significantly higher (P: 0.02) in the CC group (1.8%) compared to the letrozole group (0.2%). : There was no difference in the overall rates of major and minor congenital malformations among newborns from mothers who conceived after letrozole or CC treatments. However, it appears that congenital cardiac anomaly is less frequent in the letrozole group. The concern that letrozole use for ovulation induction could be teratogenic is unfounded based on our data.