The authors determined whether lifetime prescription drug misuse (PDM) associated with increased risks for alcohol-related problems among 18- to 34-year-old, NESARC respondents. Among 8222 "ever-drinkers," 15.4% reported ever "misusing sedatives, tranquilizers, painkillers or stimulants ... as prescriptions or from indirect sources." Outcomes were within two alcohol-related problem domains, "risk-taking behaviors," including driving while drinking, fights, injuries, and arrests, and "interpersonal troubles," including problems with jobs, family, or friends. Among all drinkers and among alcohol-dependent and cannabis-using subsamples, those reporting PDM were significantly more likely to report alcohol-related "risk-taking behaviors" or "interpersonal troubles" than were those without PDM. In adjusted analysis, young age drinking onsets, and heavy and dependent drinking independently increased these risks. Results of this cross-sectional analysis support the need for longitudinal data to more clearly define the association between drinking problems and PDM, and which can support prevention, treatment, and harm-reduction efforts for younger, multisubstance users.