In 2005, Ministry of Health introduced the Needle Syringe Exchange Program (NSEP) and Methadone Maintenance Therapy (MMT) program as a part of Harm Reduction program to combat HIV infection in Malaysia among people who inject drug (PWIDs). Expenditures were estimated approximately RM10 millions per year to establish and sustain the NSEP and MMT centres. This study examined the impact of MMT program on preventing HIV seroconversion among registered MMT clients that are people who inject drug (PWIDs), and to identify other predictors of HIV seroconversion among this group. This was a retrospective cohort study done in the state of Perak involving a total of 212 randomly selected MMT clients registered between 2008-2017 in 6 clinics. This study looks at data collected from the last ten-year cohort from baseline to follow-up. A questionnaire was used to obtain socio-demographic data, sexual and drugs abuse history. Test results for HIV were obtained from medical records. Cox regression analysis was performed to examine factors associated with seroconversion and Kaplan-Meier analysis to estimate HIV survival time. This study displayed that both Methadone take home supply (HR 10.4, 95% CI: 1.6 – 68.8) and unprotected sexual practice (HR 5.9, 95%CI: 1.1 – 31.5) shown higher risks of HIV seroconversion compared to DOTS and condom practice among MMT clients respectively. Mean survival for HIV seroconversion among MMT clients was 104.44 (95%CI: 101.85 – 107.04) months. This study provides reliable evidence that MMT program markedly reduces incidence of HIV infection among people who inject drug (PWIDs).