Objective. The primary objective of this study was to assess the association between psychiatric comorbidity and current substance use in a sample of patients with opioid use disorder (OUD) receiving opioid agonist treatment (OAT) with methadone in outpatient drug treatment centers. Secondary objectives were. (a) to examine the associations between socio-demographic and clinical characteristics and specific substance use (opioids, cocaine, alcohol, cannabis), and (b) to identify the socio-demographic and clinical factors associated with substance use based on lifetime psychiatric comorbidity status. Methods. A convenience sample of 588 patients (20% women; Mage 48.4) was recruited from eight outpatient drug treatment centers in Catalonia (Spain), which offer a comprehensive treatment approach. Dual diagnosis was assessed using the Dual Disorder Screening Interview (DDSI), and self-reported substance use (opioids, cocaine, cannabis, and alcohol) was evaluated through a specific questionnaire. Poisson regression with a log link was used to test five models adjusted for sociodemographic, clinical, and treatment variables. Results. A total of 63.5% of the patients tested positive for a lifetime dual diagnosis, and 83.5% reported substance use in the past month. No increased likelihood of opioid, cocaine, or alcohol use was observed among those with a lifetime dual diagnosis, except for cannabis use (PR = 1.29). Conclusions. Psychiatric comorbidity was not associated with current substance use in methadone-treated patients, except cannabis use. The observed patterns may be influenced by the pharmacological effects of methadone and the comprehensive treatment approach provided to patients.