Objective: Drug dependence is on the rise worldwide. The purpose of this study is to examine the association between drug dependency in pregnancy (DDP) and maternal and newborn outcomes. Methods: We carried out a population-based retrospective cohort study evaluating DDP using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 1999 to 2014. DDP was identified using ICD-9 coding. The associations between DDP and maternal and newborn outcomes were estimated using multivariate logistic regression analyses to estimate adjusted odds ratios and 95 % confidence intervals. Results: Among 14,513,587 deliveries, 50,570 were to mothers with DDP for an overall prevalence of 35 cases/10,000 deliveries. The rate of pregnancies to drug-dependent women increased during the 15-year study period, from approximately 25/10,000 in 1999 to 69/10,000 in 2014. Women with DDP were younger in age, users of tobacco, and in lower income quartiles with more pre-existing health conditions, such as diabetes and hypertension. DDP was associated with greater risk of venous thromboembolism (OR 1.60; 95 % CI, 1.45-1.76), sepsis (OR 2.94; 95 % CI, 2.48-3.49), and maternal death (OR 2.77; 95 % CI, 1.88-4.08). Neonates born to mothers with drug dependence were at higher risk of prematurity (OR 1.37; 95 % CI, 1.33-1.41), intrauterine growth restriction (OR 1.60; 95 % CI, 1.54-1.67), and intrauterine fetal death (OR 1.27; 95 % CI, 1.16-1.40). Conclusion: DDP is increasing in frequency and it is associated with maternal and newborn deaths and adverse events. Further research and public health initiatives should be undertaken to address prevention, screening, and treatment. (C) 2020 Elsevier Masson SAS. All rights reserved.