Background Depression and antidepressant treatment are widespread among women of childbearing age. Objective This study evaluates the association between duloxetine exposure during pregnancy and spontaneous and elective abortions. Patients and Methods The nationwide, observational study based on register data from Denmark included women with a recorded pregnancy in the birth register or an abortion in the patient register between 2004 and 2016. Duloxetine-exposed women were compared with (1) duloxetine non-exposed, (2) selective serotonin reuptake inhibitor (SSRI)-exposed, (3) venlafaxine-exposed, and (4) women discontinuing duloxetine before pregnancy. Exposure status was based on records of redeemed prescriptions. Cox regression with adjustments and propensity score matching was applied. Results The data from 1,019,957 pregnancies were used, including 1,212 pregnancies exposed to duloxetine. Duloxetine-exposed women had an increased hazard ratio (HR) for spontaneous abortions compared with SSRI-exposed women: propensity score matched HR 1.25 [95% confidence interval (CI), 1.00-1.57]. No increased hazard was observed for duloxetine-exposed women compared with duloxetine non-exposed: 1.08 (95% CI 0.89-1.31); venlafaxine-exposed: 1.08 (95% CI 0.82-1.41); and duloxetine discontinuers: 0.99 (95% CI 0.76-1.30). An increased HR of elective abortions was observed in duloxetine-exposed women compared to duloxetine non-exposed: 1.41 (95% CI 1.25-1.59); SSRI-exposed: 1.32 (95% CI 1.15-1.51); and duloxetine discontinuers: 1.46 (95% CI 1.23-1.75), but not to venlafaxine-exposed women: 1.09 (95% CI 0.93-1.27). Conclusion There was no increased risk of spontaneous or elective abortion associated with exposure to duloxetine. The increase risk observed for women exposed to duloxetine in comparison with SSRI-exposed for spontaneous and in comparison with all groups (except venlafaxine-exposed) for elective abortion suggested confounding.