Aims: To estimate the prevalence of exposure to acamprosate in pregnancy in New South Wales (NSW), Australia, to compare the maternal health of women exposed to acamprosate during pregnancy with non-exposed women, and to compare neonatal outcomes in neonates exposed to acamprosate in utero with non-exposed neonates. Design: A population-based retrospective cohort study, comparing maternal and neonatal health outcomes in women exposed to acamprosate during pregnancy with women with a recent history of problematic alcohol use (alcohol comparison group), and women from the general community (community comparison group) using state-wide linked health data. Setting: New South Wales, Australia. Participants: The study included women treated with acamprosate for more than 30 days during pregnancy between 2003 and 2012 (n = 54) and two matched comparison groups (1 : 3); an alcohol comparison group (n = 162) and a community comparison group (n = 162). Measurements: The prevalence of acamprosate exposure was calculated per 100 000 pregnancies. Three primary measures of maternal and neonatal health were used: maternal hospital admissions, birth weight and fetal alcohol syndrome (FAS). Findings: Exposure to acamprosate occurred in 7.7 [95% confidence interval (CI) = 6.0–9.7] in every 100 000 pregnancies. Rates of hospital admissions during pregnancy and 42 days post-partum in acamprosate-treated women were not significantly different from women in the community comparison group [adjusted rate ratio (RR) = 0.85, 95% CI = 0.65–1.11], but were significantly lower compared with the alcohol comparison group (adjusted RR = 1.26, 95% CI = 1.00–1.60). Acamprosate-exposed neonates were not significantly different from the alcohol comparison group or the community comparison group in terms of birth weight or proportion of small-for-gestational-age neonates or incidence of congenital abnormalities (including FAS). Conclusions: The prevalence of acamprosate use in pregnancy in New South Wales, Australia is low. Acamprosate exposure in utero is not clearly associated with poor maternal or neonatal health outcomes.