- Objective To evaluate whether exposure to clomiphene citrate (CC) for ovulation induction is associated with major malformations overall or with specific fetal anomalies. Design We conducted a population-based retrospective cohort study. Exposure was defined as CC dispension from 2 months before conception through the first month of pregnancy. Settings Four databases were combined: medication, birth, hospitalization, and terminations of pregnancy. Population The study included all women in southern Israel who gave birth or underwent termination of pregnancy at Soroka Medical Center, from 1998 to 2009. Methods The rates of major malformations overall and six different subcategories of anomalies were evaluated. The crude odds ratio (OR) was calculated with a 95% confidence interval (95% CI). Subsequently the adjusted odds ratio (aOR) was calculated using multiple logistic regression models controlling for maternal age, pre-pregnancy diabetes, parity, ethnicity, the calendar year in which the birth/termination of pregnancy took place, smoking, and the use of gonadotropins and progesterone. Main outcome measures Major malformations overall and specific fetal malformations by organ systems. Results Of 114 961 pregnant women, 1872 were exposed to CC. No association was detected between exposure to CC and rates of major malformations overall (aOR 1.08, 95% CI 0.88–1.32) or rates of subcategories of malformations. Exposure was not associated with anencephaly (aOR 2.27, 95% CI 0.44–11.71) or oesophageal atresia (aOR 3.681, 95% CI, 0.65–20.76). Conclusions In this large population-based retrospective cohort study, exposure to CC was not associated with an increased risk of either rates of major malformations overall or rates of specific malformations. Tweetable abstract An observational study: no increased risk for fetal malformations following exposure to clomiphene citrate.