(1) Background: Opioid use disorder (OUD) is a complex condition that can require long-term treatment. Pharmacological therapy for OUD involves treatment with opioid agonists (OMT) tailored to individual profiles. The aim of our study in daily clinical practice was to compare the profiles of patients treated with methadone (MTD) and those using buprenorphine (BHD or BHD-naloxone-NX). (2) Methods: A cross-sectional multicentre study explored the psychological, somatic and social profiles of patients with Opioid Use Disorder (OUD) following Opioid Maintenance Treatment (BHD, BHD/NX, or MTD). Descriptive and comparative analyses were performed (3) Results: 257 patients were included, a majority were men using heroin. 68% (178) were on MTD, 32% (79) were on BHD. Patients with MTD were significantly more likely to report socio-affective damage, and more likely to be younger and not to report oral or sublingual use as the main route for heroin or non-medical opioids (4) Conclusions: In daily clinical practice, regarding OUD damage, only socio-affective damage was significantly more prevalent among patients on MTD than among those on BHD in the multivariate model. Age and route of administration also differed, and our results could raise the issue of the type of OMT prescribed in case of non-medical use of prescribed opioids. These hypothesis should be confirmed in larger studies.