Fexofenadine hydrochloride is a frequently used drug for treatment of allergic conditions during pregnancy, but the fetal safety of fexofenadine use has not been well studied. To investigate the risk of adverse fetal outcomes associated with fexofenadine use during pregnancy. A nationwide registry-based cohort study was conducted on pregnancies in Denmark from January 1, 2001, to December 31, 2016. Data analysis was performed from March 21, 2019, to January 29, 2020. From a cohort of 1 287 668 pregnancies, fexofenadine use was compared with cetirizine hydrochloride use during pregnancy, matched in a 1:1 ratio on propensity scores. Distinct study cohorts and exposure time periods were applied according to each outcome analysis. Sensitivity analyses included comparing pregnancies with vs without fexofenadine exposure during pregnancy but with previous use before pregnancy and with loratadine use during pregnancy as additional comparator groups. Filled prescription for fexofenadine. Major birth defects and spontaneous abortion. Secondary outcomes were preterm birth, small size for gestational age (SGA), and stillbirth. Logistic regression was used to estimate prevalence odds ratios (ORs) of major birth defects, preterm birth, and SGA, and Cox proportional hazards regression was used to estimate hazard ratios (HRs) of spontaneous abortion and stillbirth. For the analyses of major birth defects and spontaneous abortion, a total of 2962 and 4901 pregnancies with fexofenadine use were included, respectively, matched in a 1:1 ratio with pregnancies with cetirizine use. Mean (SD) age of the fexofenadine cohort for analyses of major birth defects was 30.6 (4.8) years and, for analysis of spontaneous abortion, 30.4 (5.5) years. Infants born with major birth defects occurred in 118 pregnancies (4.0%) with fexofenadine use compared with 112 pregnancies (3.8%) with cetirizine use. Spontaneous abortion occurred in 413 pregnancies (8.4%) with fexofenadine use compared with 439 pregnancies (9.0%) with cetirizine use. Fexofenadine use during pregnancy was not associated with an increased risk of major birth defects (prevalence OR, 1.06; 95% CI, 0.81-1.37) or spontaneous abortion (HR, 0.93; 95% CI, 0.82-1.07) compared with cetirizine use during pregnancy. Preterm birth occurred in 370 pregnancies (7.5%) with fexofenadine use compared with 382 pregnancies (7.7%) with cetirizine use (prevalence OR, 0.97; 95% CI, 0.83-1.12), SGA occurred in 515 pregnancies (10.1%) with fexofenadine use compared with 523 pregnancies (10.2%) with cetirizine use (prevalence OR, 0.98; 95% CI, 0.87-1.12), and a total of 16 pregnancies (0.3%) with fexofenadine use ended in stillbirth compared with 24 pregnancies (0.4%) with cetirizine use (HR, 0.67; 95% CI, 0.36-1.27). Sensitivity analyses of the primary outcomes, including the comparisons of pregnancies with loratadine use and pregnancies unexposed to fexofenadine during pregnancy but with prior use of fexofenadine, showed similar results. Use of fexofenadine during pregnancy does not appear to be associated with an increased risk of adverse fetal outcomes.