A large population-based study, involving 290,605 pregnant women, identified 1,705 cases of neonatal abstinence syndrome for women who had filled an opioid prescription while pregnant, representing an absolute risk of 5.9 cases per 1,000 deliveries. The risk was greater for long-term prescription opioid users. The majority (88%) took them short term. Babies of women who used prescription opioids during the last trimester had a significantly higher incidence of neonatal abstinence syndrome compared with those who used them in the first two trimesters only.