Objective Studies restricted to live births may underestimate severe teratogenic effects. We address the limitation by including data from both prenatal and postnatal diagnoses of cardiac malformations. Design Register‐based study. Setting Denmark. Population 364 012 singleton pregnancies from 2007 to 2014. Methods We used data from five nationwide registries. Exposure to antidepressants was measured using redeemed prescriptions. Main outcome measures Pregnancies with cardiac malformations that end in miscarriage, termination, stillbirth, postnatal death or cardiac surgery <1 year of birth were classified as severe cardiac malformations (SCM). Propensity scores with adjusted prevalence ratios (PRs) were calculated. Results SCM were reported in 972 of 364 012 pregnancies overall and in 16 of 4105 exposed. For venlafaxine, the PR for SCM was 2.13 (95% confidence interval CI 0.89–5.13), 1.73 (95% CI 1.08–2.77) for other cardiac malformations, and there was a cluster of hypoplastic left heart syndromes (HLHS) (crude PR 17.4 95% CI 6.41–47.2), none of which ended in a live birth. For HLHS, the absolute risk increase was 4.4/1000 and the number needed to harm was 225. For selective serotonin reuptake inhibitors, the PRs were 1.09 (95% CI 0.52–2.30) and 1.38 (95% CI 1.00–1.92) for SCM and other cardiac malformations, respectively. Conclusions Pregnancy exposure to venlafaxine is associated with an increased risk of severe cardiac malformations but with a low absolute risk. Potential mechanisms include direct effects or confounding by indication. Venlafaxine exposure is a marker for risk pregnancies for which fetal echocardiography may be considered. Tweetable Exposure to venlafaxine is associated with an increased risk of cardiac malformations but with a low absolute risk. Tweetable Exposure to venlafaxine is associated with an increased risk of cardiac malformations but with a low absolute risk.