Simultaneous co-ingestion of prescription medication (e.g., opioid, tranquilizer/sedative, stimulant) and alcohol is associated with overdose and elevated substance use, but no studies have examined prescription drug misuse (PDM) and alcohol co-ingestion in U.S. young adults (18-25 years), despite the high rates of PDM in this age group. We used the 2015-19 National Survey on Drug Use and Health (young adult N = 69,916) to examine prevalence of past-month PDM-alcohol co-ingestion, PDM characteristics, and sociodemographic, physical health, mental health, and substance use correlates. Logistic regression examined correlates, comparing those without past-year PDM, those with past-year but not past-month PDM, those with past-month PDM without alcohol co-ingestion, and those with past-month PDM and alcohol co-ingestion. An estimated 585,000 young adults engaged in any past-month PDM-alcohol co-ingestion, or between 32.7% (opioids) and 44.6% (tranquilizer/sedatives) of those who were engaged in past-month PDM. Co-ingestion varied by educational status and was more common in males and white or multiracial young adults. All PDM-involved groups had elevated odds of suicidal ideation and other psychopathology, but substance use and substance use disorder (SUD) odds were significantly higher in young adults with co-ingestion, versus all other groups. To illustrate, 41.1% with opioid-alcohol co-ingestion had multiple past-year SUDs, versus 2.0% in those without past-year PDM. Young adults with co-ingestion are particularly likely to have problematic alcohol use and higher rates of SUD. Counseling about the risks of PDM-alcohol co-ingestion and screening for co-ingestion among those at risk are warranted to limit poor outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).