PROJECT SUMMARY Over 4 million births occur in the United States each year, and opioid prescribing for acute pain during pregnancy and childbirth is common and highly variable. Guidelines to direct opioid prescribing during pregnancy and birth are sparse, leading to excessive prescribing and increasing the risk of opioid overdose, addiction, diversion, and persistent opioid use. In this 3 year study, we will create evidence-based, patient- centered guidelines to support acute postoperative pain management for pregnant individuals during childbirth and surgery. We will examine the effectiveness of implementing these guidelines on clinical and patient- reported outcomes in a large, state-wide consortium of 68 hospitals within the Collaborative Quality Improvement programs in Michigan. We will convene a national panel of patients, providers, reproductive justice advocates, health equity experts, and health system leaders to guide all activities. First, we will use the RAND/UCLA Appropriateness methodology to merge a systematic literature review with expert opinion to create provider- and patient-facing guidelines that direct opioid prescribing, integrate opioid-alternatives and considerations for unique populations (high-risk pregnancies, comorbid conditions, prior opioid exposure, opioid and substance use disorders), and include best practices to promote health equity and patient- centeredness (Phase 1). We will create tailored strategies for CPG dissemination and implementation using state of the art techniques in implementation science at the national and facility level (Phase 2). Finally, we will conduct an enhanced, non-responder randomized trial across 68 hospitals in Michigan to determine the effectiveness of CPGs that inform opioid prescribing during peripartum care as well as the impact of innovative, adaptive implementation interventions at the hospital level (Phase 3). Our primary outcomes will include the rate and amount of opioid prescribed among pregnant individuals during surgery and childbirth. We will also examine patient-reported outcomes (e.g., postoperative pain, opioid use, satisfaction) as secondary outcomes. We will specifically examine the effect of CPGs across marginalized groups to ensure that guideline implementation does not exacerbate existing disparities in postoperative pain management. Our findings will directly impact obstetric care by rigorously creating pragmatic, patient-centered guidelines to direct postoperative opioid prescribing that are tailored to the unique needs of pregnant and birthing individuals. Given the robust network of Collaborative hospital systems caring for a diverse cohort of pregnant individuals in Michigan, our findings will provide critical evidence to direct optimal strategies for guideline dissemination and implementation across the United States.