Protective behavioral strategies (PBS) are behaviors that individuals use to mitigate harm related to risky behaviors. Though measures have been validated to assess alcohol- and cannabis-specific PBS use, an opioid-specific PBS measure has yet to be validated. The present study developed and validated a tool to assess the extent of PBS employed by individuals who use licit and/or illicit opioids. We recruited a community sample of adults who endorsed past-month opioid use (n = 345) via online platforms to complete a baseline survey, and 277 participants (80.2%) also completed the 1-month follow-up survey. From PBS measures of other substances, harm reduction strategies found in the literature, and expert feedback, we developed the 60-item Opioid Protective Behavioral Strategies Scale (OPBSS). We removed 14 items based on item and exploratory factor analyses, resulting in 46 retained items. A two-factor solution was supported: strategies focused on managing opioid use (Controlled Opioid Use) and preventing opioid-related harm (Serious Harm Reduction). The OPBSS subscales demonstrated high internal consistencies, fair-to-excellent test-retest reliability, significant positive associations with PBS measures for other substances, and robust associations with risky opioid use and opioid-related negative consequences, both concurrently and prospectively when controlling for other opioid characteristics. The 46-item OPBSS has promising psychometric properties. Importantly, more opioid PBS predicted less risky opioid use and related consequences, suggesting that opioid PBS may be a beneficial opioid prevention effort. However, additional psychometric work is needed to determine which PBS are most suitable for populations with distinct opioid use patterns. (PsycInfo Database Record (c) 2024 APA, all rights reserved).