Context: Using buprenorphine in primary care is a proven strategy to treat opioid dependence and use disorder. Treatment with buprenorphine includes induction (beginning treatment), stabilization, and maintenance. Guidelines support induction at the clinic (observed), telehealth (observed by phone or video), or at home (unobserved). Important clinical differences between induction methods might influence successful transition to stabilization and treatment. While both home and office induction are evidence based, no randomized comparative effectiveness research (CER) study provides evidence to support decisions about which option is the best fit for individual patients. Objective: In partnership with community members from around United States, conduct a multicenter, randomized, CER trial to answer the question from patients and clinicians: What is the best way for me/this patient to start treatment for this patient at this time? Design: Pragmatic, community-engaged, CER trial. Setting: 100 primary care and mental health care practices in the United States associated with the State Networks of Colorado Ambulatory Practices and Partners and American Academy of Family Physicians National Research Network. Population studied: 1200 patients seeking treatment with buprenorphine for opioid dependence and use disorder and practice members. Outcomes Measures: Primary outcomes include number of days in treatment and number of days using other opioids. Secondary outcomes include quality of life and social determinants of health. Covariates and potential moderators include appeal and severity of substance use, treatment history, executive function, and social support and isolation. Results: 69 practices have been recruited thus far to three study waves. Patient recruitment began in May 2021. Current practice and patient characteristics will be reported. Conclusions: The HOMER study will generate pragmatic results from real-world settings. Findings will be immediately applicable to clinicians, training programs, and policy makers to fill a critical gap in the evidence that can lead to increased access to and effectiveness of MAT – primary care practices informing primary care practice.