The aims of this study were to describe and compare the epidemiology of acute poisoning hospital discharges in women of reproductive age and during pregnancy (aged between 15 and 44) to include the incidence rate, risk factors, substances involved, rates of intentional versus unintentional poisonings, and in pregnant women, distribution over trimesters. Through a cohort study design, the California patient discharge dataset and linked vital statistics-patient discharge database were used to identify cases of acute poisoning hospital discharges from 2000 to 2004 among women of reproductive age and among pregnant women. Odds ratios (OR) were calculated to identify risk factors using logistic regression. Of 4,436,019 hospital discharges in women of reproductive age, 1% were for an acute poisoning (115.3/100,000 person-years). There were 2,285,540 deliveries and 833 hospital discharges for an acute poisoning during pregnancy (48.6/100,000 person-years). Pregnancy was associated with a lower risk of acute poisoning (OR = 0.89, P = 0.0007). Poisonings were greatest among young black women regardless of pregnancy status and among those with substance abuse or mental health problems. Analgesic and psychiatric medications were most commonly implicated. The majority of poisonings among women of reproductive age (69.6%) and among pregnant women (61.6%) were self-inflicted. Efforts to reduce acute poisonings among women of reproductive age should include education regarding the use of over-the-counter medications and interventions to reduce self-inflicted harm.