Objective: Despite protective behavioral strategies (PBS) being an important part of alcohol-prevention programs, use of PBS is suboptimal, and research is needed to determine factors associated with the use and non-use of PBS. The present study examined daily-level associations between situational familiarity (i.e., familiarity with locations and people) and the use of alcohol-related PBS among adolescents and young adults. Method: Participants (analysis n = 564, 55.1% female, 45.2% White, non-Hispanic, ages 15 to 25 years, M = 21.07 years [SD = 2.79]) were part of a longitudinal ecological momentary assessment burst study on cognitions and alcohol use. Mixed-effects Poisson models were used to analyze data for engagement in PBS (i.e., serious harm- reduction, stopping/limiting, and manner-of-drinking PBS). Results: Within-person results indicated that when participants had elevated (i.e., higher than their own average) familiarity with their location, they were less likely to use serious harm-reduction PBS (rate ratio [RR] = 0.94, p <.001) and stopping/limiting PBS (RR = 0.95, p < .001). Results showed that on drinking days with elevated familiarity with people, individuals were more likely to use serious harm-reduction PBS (RR = 1.03, p = .01). There were no significant daily-level associations between familiarity with people or location and manner-of-drinking PBS. Conclusions: The study suggests that PBS use, particularly for serious harm-reduction and stopping/limiting strategies, varies among adolescents and young adults based on familiarity with location and people. Alcohol-prevention interventions, including just-in-time interventions, should consider how to promote PBS use, particularly in familiar locations and with less familiar people. (J. Stud. Alcohol Drugs, 86, 115-123, 2025)