Importance: The prevalence of cannabis use in pregnancy is rising and is associated with adverse perinatal outcomes. In parallel, combined prenatal use of cannabis and nicotine is also increasing, but little is known about the combined impact of both substances on pregnancy and offspring outcomes compared with each substance alone.

Question: Is in utero exposure to cannabis and nicotine in combination associated with greater adverse outcomes than exposure to either substance alone during pregnancy?

Findings: In this population-based cohort study of more than 3.1 million pregnant individuals, combined use of cannabis and nicotine products in pregnancy was associated with an increased risk of maternal and neonatal morbidity compared with use of either substance alone, including infant and neonatal death, infants small for gestational age, and preterm delivery.

Meaning: These findings suggest that more effective public health measures and counseling prior to conception and during pregnancy are warranted to mitigate the potential for adverse offspring outcomes from combined prenatal cannabis and nicotine use.