Adverse Childhood Experiences (ACEs) are potentially traumatic events that occur in childhood, such as experiencing violence, abuse, or neglect; witnessing violence in the home; and having a family member attempt or die by suicide. Aspects of a child’s environment can undermine their sense of safety, stability, and bonding, such as growing up in a household with substance misuse, mental health problems, or instability due to parental separation or incarceration of a parent or caregiver. Data show that approximately two-thirds of adults in the U.S. report having experienced at least one ACE and 1 in 6 adults have reported 4 or more ACEs before the age of 18. More than two decades of research has documented the effects of ACEs on health, wellbeing, and opportunity across the lifespan. A longstanding and robust body of research links ACEs to increased risk for substance use and substance use disorders (SUDs). More recent research confirms that ACEs are a strong risk factor specifically for both opioid and methamphetamine and other stimulant use. Thus, preventing ACEs is a potentially potent strategy to reduce substance use and its related harms. The proposed presentation will explore this empirical relationship between ACEs and substance use and SUD, with particular focus on CDC’s approach to addressing the intersection of risk and prevention for both ACEs and substance use. The presentation will also describe CDC’s ACEs prevention resource – Preventing Adverse Childhood Experiences: Leveraging the Best Available Evidence – that offers multiple strategies to support comprehensive policies, programs, and practices that can be implemented to prevent ACEs and mitigate their harms.