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.