Colombia has experienced a dramatic increase of heroin use in the last 3 decades, stablishing the first methadone maintenance treatment (MMT) program in 2004. Although international evidence indicates that MMT has important benefits for people with opioid use disorder, technical and logistical difficulties have been identified in Colombia that can compromise the effectiveness of this treatment modality. In this cross-sectional study, a total of 148 subjects with opioid use disorder were interviewed in the city of Armenia (Colombia) using the Opiate Treatment Index, comparing the drug use, social functioning, human immunodeficiency virus risk behaviors, criminal activity, and the physical/mental health among subjects involved in MMT and those not receiving treatment. Despite the above-mentioned difficulties, subjects participating in MMT reported less illegal substance use (specifically heroin and basuco), less human immunodeficiency virus risk behaviors, better social functioning, less criminal activity, and less physical and mental health problems than those not receiving treatment. In addition, subjects involved in MMT reported a daily use of heroin and lower than recommended dosages of methadone. Therefore, Colombia should continue expanding MMT programs across the country, integrating the available harm reduction strategies and providing continuous training for health professionals in charge of these programs.