BACKGROUND: Prescription drugs account for approximately 11% of national health expenditures. Prior research on adverse childhood experiences (ACEs), which include common forms of child maltreatment and related traumatic stressors, has linked them to numerous health problems. However, data about the relationship of these experiences to prescription drug use are scarce. METHOD: We used the ACE Score (an integer count of 8 different categories of ACEs) as a measure of cumulative exposure to traumatic stress during childhood. We prospectively assessed the relationship of the Score to prescription drug use in a cohort of 15,033 adult HMO patients (mean follow-up: 6.1 years) and assessed mediation of this relationship by documented ACE-related health and social problems. RESULTS: Nearly 1.2 million prescriptions were recorded; prescriptions rates increased in a graded fashion as the ACE Score increased (p for trend < 0.0001). Compared to persons with an ACE Score of 0, persons with a Score > or = 5 had rates increased by 40%; graded relationships were seen for all age groups (18-44, 45-64, and 65-89 years) (p for trend < 0.01). Graded relationships were observed for the risk of being in the upper decile of number of classes of drugs used; persons with scores of > or = 5 had this risk increased 2-fold. Adjustment for ACE-related health problems reduced the strength of the associations by more than 60%. CONCLUSION: ACEs substantially increase the number of prescriptions and classes of drugs used for as long as 7 or 8 decades after their occurrence. The increases in prescription drug use were largely mediated by documented ACE-related health and social problems.