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Mental health problems such as depression and anxiety are highly prevalent among people who use drugs (PWUD). The positive psychological intervention (PPI) is a newly developed method which has been applied successfully in the general populations to improve mental health status. In this study, we designed a randomized controlled trial (RCT) to test the feasibility and efficacy of the PPI in improving mental health status of PWUD attending methadone maintenance treatment (MMT). A total of 140 MMT users were randomly allocated into the intervention group (n = 70) which carried on the intervention (documenting "Three Good Things" every day for 2 weeks) and the control group (n = 70) which received booklets about mental health. Baseline, 2-week, 1-month, and 3-month follow-up interviews were conducted. Generalized estimating equations for repeated measurements were used to examine the efficacy of intervention. Data showed that at baseline, the prevalence of probable depression was 75.4% and 73.9% in the two groups respectively, while the prevalence of anxiety was 56.5% and 45.7%, and the prevalence of low satisfaction with life was 70.0% and 52.2%. About 60% of the intervention group members adhered to at least 50% of intervention. In the multivariate model, PPI was not significantly associated with probable depression (ORa = 0.75, 95% CI 0.27–2.12), anxiety (ORa = 0.99, 95% CI 0.47–2.06), or low satisfaction with life (ORa = 1.54, 95% CI 0.65–3.65). Efficacy of PPI was not observed in this study while PPI intervention is potentially feasible among some PWUD. Efficacy of PPI could be further test in studies with other innovative ways and longer intervention period. [ABSTRACT FROM AUTHOR]