Methadone maintenance treatment (MMT) programs have been used worldwide to reduce the number of drug users and for HIV prevention; however, evidence of their effectiveness in mountainous areas is limited. This study aimed to identify changes in substance abuse and sexual practices among MMT patients after treatment in three Vietnamese mountainous provinces. A survey on risk behaviors was conducted among 300 drug users in six MMT clinics prior to and following one year of MMT. Cramér's effect size of changes was extrapolated to justify the magnitude of the intervention's effectiveness. A generalized estimation equation was used to find the factors associated with respondents' substance use and sexual risk behavior. While drug-related risk behaviors were significantly reduced, alcohol and sex-related behaviors remained risk factors for HIV in this group. Additionally, condom use was common among participants at both time points, but not among those having sex with sex workers. Socio-economic characteristics of ethnic, education, occupation, as well as drug use history influenced the possibility of engaging in drug use and/or sexual risk behavior following treatment. Further emphasis on managing these among MMT patients is required, potentially by providing integrated services including smoking and drinking counseling and condom use promotion in accordance with MMT.