Methadone maintenance treatment (MMT) has been associated with many positive outcomes, including lowering the prevalence of HIV infections among drug users in Malaysia since its implementation. However, relapse among methadone clients remains a challenging issue for health care providers. Studies investigating relapse at MMT facilities are limited in Malaysia. This present study primarily aimed to determine the prevalence of relapse as well as explore the relationship between self-efficacy and relapse among MMT clients. This cross-sectional study involved 129 MMT clients recruited using the convenient sampling method at a primary health clinic in Kuala Muda, Kedah. The study instruments used were the validated Malay version of the Smoking and Substance Involvement Screening Test (ASSIST) and the General Self- Efficacy Scale. The data collected was analyzed with SPSS version 23. The results showed that the prevalence of relapse was 64.3% (n = 83), and the most abused illicit substances by relapse participants were opioids (75.9%), followed by amphetaminetype stimulants (38.6%), cannabis (10.8%), and ketum (7.2%). The independent sample T-test results showed that the self-efficacy level of the non-relapse group was significantly higher than that of the relapse group. The Pearson correlation analysis also demonstrated that there was a strong negative correlation between self-efficacy and relapse among the participants (r =-.736, p =.001). In conclusion, the prevalence of relapse among participants was high, and a higher level of self-efficacy is associated with lower relapse. Psychosocial interventions to enhance self-efficacy levels among MMT clients are recommended in clinical practice and future research.