There is an urgent need to address sub-optimal retention in office-based buprenorphine (BUP) and expand access to methadone outside of opioid treatment programs (OTP). Meta-analyses and CTN 0027 demonstrate that retention in methadone is higher than BUP. Factors contributing to low retention in office-based BUP may include lower agonist activity, poor BUP adherence, polysubstance use, insufficient behavioral services, patient preference, and co-occurring conditions (i.e., chronic pain). Clinicians currently have 2 options for patients not optimally benefitting from office-based BUP. They can attempt to enhance BUP services or refer the patient to an OTP for methadone. We propose to evaluate a needed new option – office-based methadone prescribing (under a research exemption to the Controlled Substance Act) with methadone dispensing at a pharmacy or medication dispensing unit. Simultaneously, access to medications for opioid use disorder in the United States is characterized by profound racial and urban/rural disparities which could also be addressed by office-based methadone. We propose to conduct a 6 site hybrid effectiveness implementation trial to compare: 1) Office-based methadone where the current office-based BUP prescriber manages a switch to and continuation of methadone in partnership with a local methadone dispensing facility (pharmacy or other OTP-affiliated medication unit) versus; 2) Enhanced BUP where the office-based BUP provider continues BUP treatment while providing enhanced behavioral treatment and/or implementing strategies to address adherence if indicated (directly observed therapy, thrice-weekly BUP, or extended-release BUP), in 520 patients not optimally benefiting from office-based BUP. In Aim 1 we will train 6 large office-based BUP sites to provide methadone with offsite administration/dispensing. In Aim 2 we will evaluate the comparative effectiveness of office-based methadone versus Enhanced BUP on treatment retention at 6 months after randomization. In Aim 3 we will use mixed methods and an implementation science framework to identify implementation barriers and facilitators at the patient, provider and health- systems level for office-based methadone. Our team comprising early stage investigators, stakeholders and people with lived experience, established researchers trained in primary care, addiction medicine/psychiatry, clinical trials, disparities, qualitative research and implementation science has experience conducting research in the CTN, evaluating office-based buprenorphine, office-based methadone and pharmacy-based dispensing of methadone. This would be the first study to: 1) capitalize on experienced BUP prescribers who would learn to prescribe methadone; 2) evaluate the effectiveness office-based methadone in patients at high risk for not being retained in BUP; and 3) assess patient and system barriers and facilitators to office-based methadone.