PROJECT SUMMARY At least 15.4 million opioid prescriptions in the United States are provided each year during surgical care. Excessive and risky perioperative opioid prescribing patterns are common and increase the risk of opioid overdose, addiction, diversion, and persistent opioid use. To mitigate these harms, policymakers and payers in most states have enacted policies that restrict opioid prescribing for acute pain or mandate clinicians to review prescription drug monitoring program databases before prescribing opioids (PDMP use mandates). To date, few studies have rigorously assessed the intended and unintended effects of these policies in the context of surgical care. In this 4-year study, we will use quasi-experimental methods to examine the impact of opioid prescribing limits and PDMP use mandates on perioperative opioid prescribing, high-risk prescribing, opioid-related adverse events, and patient-reported outcomes. First, we will use commercial, Medicare, and Medicaid claims databases to evaluate the effect of state opioid prescribing limits and to assess variation in effects by policy feature, patient population, procedure, and prescriber (Aim 1). Second, we will evaluate the effect of state PDMP use mandates and examine heterogeneity in effects using the same claims databases (Aim 2). Finally, we will determine the impact of a major Michigan insurer’s opioid prescribing limit and Michigan’s PDMP use mandate on opioid prescribing and patient-reported outcomes after surgery, using a novel linkage between a statewide registry of surgical patients and the state PDMP database (Aim 3). Our findings will directly inform efforts to mitigate morbidity from perioperative opioid prescribing and close critical knowledge gaps needed to optimize future policy design. For example, if opioid prescribing limits and PDMP use mandates have reduced perioperative opioid prescribing with minimal unintended effects, policymakers should consider implementing these policies more broadly. However, if the policies have not reduced perioperative opioid prescribing or have had substantial unintended effects, other approaches may be needed. Ultimately, this proposal will contribute to the development of well-designed policies that balance the need for safe opioid prescribing with the need for effective postoperative pain management.