OBJECTIVES: This study aims to compare the HRQoL between patients receiving methadone maintenance therapy (MMT) program with those in the rehabilitation program. METHODS: This was a cross-sectional study involving 400 randomly selected patients from two primary and secondary hospitals and one rehabilitation centre (PUSPEN) in northern part of Malaysia. Consented patient was interviewed to collect their socio-demography, drug consumption and quality of life information. The quality of life was measured by using EQ-5D and EQ-VAS questionnaires. Their quality of life scores were then compared using independent t-test. RESULTS: Majority of the participants were male with mean age 38.49 (SD=9.6) in MMT group and 34.77 (SD=8.6) in rehabilitation group. Mean duration of treatment for MMT group was 17.5 months (SD=15.74) and rehabilitation group was 7.8 months (SD=3.52). EQ-5D score was significantly (P = 0.01) higher among MMT participants (mean=0.783, SD=0.190) compared to those in rehabilitation program (mean=0.707, SD=0.227). Participants receiving MMT treatment also had lesser problems in mobility (10.5% versus 21%; p <0.01), normal activity (6.5% versus 15%; p <0.05) and anxiety (54.5% versus 71%; p <0.001). There was no statistically difference found between the groups in self care activity and pain dimensions. However, EQ-VAS score was significantly lower in MMT group compared to rehabilitation group [65.5 (SD=17.9) versus 73.5 (SD=17.6), p<0.001]. CONCLUSIONS: This study shows that treatment for patient with substance use disorder with MMT program can provide a better quality of life compared to rehabilitation program (PUSPEN). Variation seen between EQ-5D and EQ-VAS scores suggest that patients might perceived their health worst than the general population value.