Objectives: Women with Down syndrome (DS) suffer from several health issues, however, their fecundity is not affected. Despite that, there are no studies in the literature to address pregnancy, delivery, or neonatal outcomes among women with DS. Design: We conducted a retrospective study using the Health Care Cost and Utilization Project-Nationwide Inpatient Sample Database over 11 years from 2004 to 2014. Methods: A delivery cohort was created using ICD-9 codes. ICD-9 code 758.0 was used to extract the cases of maternal DS. Pregnant women with DS (study group) were matched based on age and health insurance type to women without DS (control) at a ratio of 1:4. A multivariant logistic regression model was used to adjust for statistically significant variables (P-value < 0.5). Results: There were a total of 9,096,788 deliveries during the study period. Of those, 185 pregnant women were found to have DS. The matched control group was 740. Maternal pregnancy risks mostly did not differ between those with and without DS including pregnancy-induced PIH, gestational diabetes, preeclampsia, PPROM, chorioamnionitis, cesarean section, operative vaginal delivery, or blood transfusion (P >0.05, all). However, they were at extremely increased risk of delivering prematurely (aOR 3.86, 95% CI 1.25-11.93), and to have adverse neonatal outcomes such as small for gestational age (aOR 13.13, 95% CI 2.20-78.41), intrauterine fetal demise (aOR 20.97, 95% CI 1.86-237.02), and congenital anomalies (aOR 9.59, 95% CI 1.47-62.72). Conclusion: Women with DS should be counseled about their increased risk of premature delivery and adverse neonatal outcomes.