Background: The burden of drug use is growing rapidly in Low- and Middle-Income countries (LMICs) with access to coastlines and most major cities;Tanzania is not exception. Methadone Assisted Treatment (MAT) has a potential to reduce addiction and therefore health and quality of lives. MAT is known to improve health related quality of life and it is essential in addressing a number of drug use related challenges among People Who Inject Drugs (PWIDS). Evidence on the profiles of Health Related Quality of Life (HRQOL) among PWIDS who are in treatment programmes particualry MAT services, is scanty in Zanzibar, Tanzania, Objectives: To determine HRQOL and associated factors among PWIDS receiving MAT Services in Zanzibar, Tanzania. Methods: This was a cross-sectional study conducted in Unguja, Zanzibar from July to August 2019. A total of 376 PWIDS attending Kidongo Chekundu MAT clinic were randomly selected and enrolled in the study. Data were electronically collected using Open Data Kit (ODK) programme during face-to-face interviews with PWIDS HRQOL was measured using the WHO's Quality of Life questionnaire Descriptive and binary logistic regression analyses were used to describe and determine factors independently associated with HRQOL. Results: Of the 376 PWIDS enrolled in this study, Vast majority (92.6%) were male. The mean age of participants at enrollment was 39 (± standard deviation (SD) 8.9). Slightly more than one third (45.5%) were single, 56.4% have a secondary school education level. Slightly more than two third (82.7%) were employed, 42% reported living at Magharibi B districts. High proportion were on MAT services for more than one year (70.2%); had good adherence to MAT services (79%), and were receving 50 – 99 mg of methadodone dose per day (51.1%).The majority of PWIDS (82%) had of high HRQOL. Employed PWIDS [AOR=5.36; 95%CI (1.51, 19.04); p=0.009], and PWIDS who were in the middle wealth quintile [OR=24.15; 95%CI (2.01, 290.30); p=0.012] were more likely to have better HRQOL. Conclusion: In general, PWIDS on MAT services have good HRQOL in Zanzibar. Being employed or having better economic status among were associated with better HRQOL. To effect this there is a need to strengthen multisectoral collaborations, integrated and comprehensive MAT services within the clinic and other related areas with all relevant stakeholders so as to improve health related quality of life among PWIDS.