Objectives Smoking in pregnancy is associated with an increased risk of preterm birth (PTB), intrauterine growth restriction, placental abruption and perinatal death. The association between smoking and other delivery outcomes, such as chorioamnionitis, mode of delivery or post partum hemorrhage (PPH), however, is insufficient as only few studies addressed these issues. The aim of the study was to evaluate the association between prenatal smoking and delivery outcomes in a large database, while controlling for confounding effects. Methods A retrospective population-based study using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP‐NIS). A dataset of all deliveries between 2004 and 2014 (inclusively) was created. Our control group included all pregnant women who did not smoke during pregnancy, which was compared to pregnant women who smoked. A multivariate logistic analysis was conducted, adjusting for any statistically significant confounding effects. Results Our study identified 9,096,788 births between 2004 and 2014. Of which, 443,590 (4.8%) had a documented diagnosis of smoking. A significantly higher risk was found for PTB (odds ratio 1.39, CI 1.35–1.43), preterm premature rupture of membranes (odds ratio 1.52, CI 1.43–1.62) and small for gestational age (SGA) neonates (odds ratio 2.27, CI 2.19–2.35). The risks of preeclampsia (odds ratio 0.82, CI 0.78–0.85), chorioamnionitis (odds ratio 0.88, CI 0.83–0.4), PPH (odds ratio 0.94 CI 0.9–0.98) and operative vaginal delivery (odds ratio 0.9, CI 0.87–0.94) were lower among smokers. Conclusions This large database confirms the findings of previous smaller studies, according to which smoking decreases the risk of preeclampsia while increasing the risk of PTB and SGA neonates. The current study also revealed a decreased risk for PPH as well as for chorioamnionitis among pregnant smokers.