Background: Patients disengaged from HIV care, e.g., missed medication pick-ups, not attending physician visits, account for >70% of new HIV infections. Re-engaging and sustaining engagement is essential to controlling the HIV pandemic. This study tested a physician-delivered evidence-based intervention, Motivational Interviewing (MI), to improve health outcomes, adherence to antiretroviral therapy (ART), HIV virologic suppression, CD4+ count, retention in HIV care, and self-efficacy among patients in Argentina disengaged from care. Methods: Regional clinics (n = 6) were randomized to condition, MI Intervention, Enhanced Standard of Care (ESOC), and recruited N = 360 disengaged patients disengaged from HIV care. Participants were assessed at baseline, 6, 12, 18, and 24-months. Indirect effects from condition to main outcomes were examined using patient–provider relationship as a mediator. Findings: Participants were an average age of 39·15 (SD = 10·96), 51% were women; intervention participants were older (p = ·019), and more ESOC participants were women (60% vs. 42%, p = ·001). There was an indirect effect of condition on ART adherence (B = 0·188, p = ·009), HIV viral load (B = -0·095, p = ·027), and self-efficacy (B = 0·063, p= ·001), suggesting the intervention was associated with improved patient–provider relationships, which was in turn associated with increased ART adherence, lower HIV viral load, and higher self-efficacy. Intervention participants reported greater satisfaction with patient-provider relationships (p = ·005), higher ART adherence (p = ·02), CD4+ counts NS, and lower HIV viral load (p = ·015). Retention in HIV care was higher at 12 months but not sustained. Interpretation: Physician-delivered MI enhanced patient-provider relationship, self-efficacy, and ART adherence, and reduced HIV viral load in patients disengaged from HIV care. Implementation of sustained collaborative patient-centered MI in HIV clinical settings could strengthen patient-provider relationships and re-engage patients in their own care. Trial Registration: This study was registered at clinicaltrials.gov, NCT02846350. Funding: National Institutes of Health. Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: This study was approved by the Institutional Review Board at the University of Miami Miller School of Medicine and at by each participating center.