This study is a multi-site open-label randomized comparative effectiveness trial of a 28-day formulation of extended-release buprenorphine (XR-BUP) versus treatment as usual (TAU) for hospitalized patients with a moderate or severe opioid use disorder (OUD) seen by an addiction consultation service (ACS) and agreeing to initiate a medication for OUD (MOUD). Participants will be randomly assigned to XR-BUP or TAU to be received within 72 hours of anticipated hospital discharge. Follow up will occur at approximately 34, 90, and 180 days following hospital discharge.

The study will randomize approximately 314 hospitalized men and women ages 18 years and older with opioid use disorder (OUD) moderate or severe and who have not been taking prescribed medication for OUD (MOUD) for 14 days or more prior to hospitalization. Eligibility will be determined over one or more assessments during the index hospitalization. Once eligibility has been determined, participants will be randomized 1:1 to either a single injection of extended-release buprenorphine or TAU, which will include methadone, sublingual buprenorphine, or naltrexone. Connection to OUD care and ongoing MOUD following hospitalization will be per community standard. Participants will be assessed for engagement in OUD treatment by the presence of a legitimately prescribed MOUD on day 34 following hospital discharge. Further outcomes will be assessed at 90 and 180 days following hospital discharge.

Inclusion Criteria:

1. Hospitalized.
2. At least 18 years of age.
3. Meet Diagnostic and Statistical Manual (DSM-5) criteria for moderate or severe OUD.
4. Willing to initiate MOUD, including buprenorphine.
5. Able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study.

Exclusion Criteria:

1. Anticipated length of stay less than 24-hours as determined by the ACS

2. Affected by a serious medical, psychiatric, or substance use disorder that, in the opinion of the study physician, would make it unsafe to participate in the study or may prevent collection of study data. This may include:

   1. Disabling terminal diagnosis for which discharge from hospital is not anticipated.
   2. Disabling terminal diagnosis for which hospice care is being sought.
   3. Severe alcohol or benzodiazepine use disorder that is anticipated to require complex medical detoxification which cannot be completed prior to randomization.

3. Taking a long-acting opioid other than buprenorphine (e.g., methadone, extended-release oxycodone, extended-release morphine) in the three consecutive days prior to randomization.

4. Liver enzyme tests (Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT)) more than 5 times upper limit of normal or chronic decompensated liver disease.

5. Currently pregnant.

6. Known allergy to buprenorphine or components of Atrigel delivery system.

7. Receipt of MOUD in the 14 days prior to hospitalization as maintenance treatment; however, patients may have received MOUD for withdrawal management during or prior to hospitalization at the time of enrollment.

8. Are currently in jail, prison or other overnight facility as required by court of law and/or is considered a prisoner under local law or is under current terms of civil commitment or guardianship.

9. Previously randomized as a participant in the study - individuals may only be enrolled and randomized once.

Data will be transmitted by the study Data and Statistics Center to the designated party for de-identification, posting, storing, and archiving on the National Institute on Drug Abuse (NIDA) Data Share website. Data Share is an online repository of data from studies funded by the National Institute on Drug Abuse. De-identified individual participant data is expected to be made available.

The data will be shared after the primary outcome paper has been accepted for publication, or 18 months after data lock, whichever comes first. The data will remain indefinitely.

Data from this study will be available to researchers on the website https://datashare.nida.nih.gov/ after the study is complete and the data is analyzed. This website will not include information that can identify individual study participants.The following information will be posted: Study protocol, reference to study publication of primary outcome, data sets (SAS and ASCII ), annotated case report forms, define file (also known as Data Dictionary), study-specific de-identification notes. Prior to downloading any study data, the user will be prompted to complete a registration agreement for data use. Users will have to register a name and valid e-mail address in order to download data and to accept their responsibility for using data in accordance with the NIDA Data Share Agreement.