Abstract Background Data on diuretic use during pregnancy are limited and show varying results. Therefore, it remains unsure whether they can be safely used. Purpose Our study aims to evaluate the perinatal outcomes after in-utero diuretic exposure. Methods The Registry of Pregnancy and Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with structural heart disease. Outcomes were compared between women who used diuretics during pregnancy versus those who did not. Multivariable regression analysis was used to assess the impact of diuretic use on the occurrence of congenital abnormalities and fetal growth, after adjustment for potential confounders. Results Diuretics were used in 382 (6.7%) of the 5739 ROPAC pregnancies, most often furosemide (n=332, 86%). Women who used diuretics during pregnancy, compared to those without, were older (30.9 vs 29.4 years; p<0.001), had a higher BMI (25.3 vs 23.9 kg/m2; p<0.001), were more likely to live in a low-middle income country (63.1% vs 38.1%; p<0.001), and more likely to have chronic hypertension (9.9% vs 6.4%; p=0.007), atrial fibrillation/flutter (7.1% vs 1.5%; p<0.001), signs of heart failure (27.2% vs 9.2%; p<0.001) and/or an estimated LVEF below 40% (19.9% vs 3.3%; <0.001). Diuretic use during the first trimester was not independently associated with fetal or neonatal congenital abnormalities (OR 1.30; 95% CI 0.66-2.55). After adjustment for confounders, diuretic use during pregnancy was not independently associated with small for gestational age (OR 1.36; 95% CI 0.97-1.91). Conclusions Based on our data, diuretics can be used safely during pregnancy and discontinuation of diuretics prior or during pregnancy in women with appropriate indication seems not to be necessary. However, for treatment of systemic hypertension, alternative antihypertensive agents with more safety data regarding perinatal outcomes, such as labetalol or nifedipine, are preferred.