A cohort of 516 patients at two community-based methadone maintenance treatment (MMT) clinics in Guangdong province, China, was interviewed at initiation of treatment and at 1, 3, and 6 months of follow-up to collect demographic information, drug use experience, social support, and changes of quality of life (QOL) over treatment. Covariance analysis and generalized estimation equation model were used to compare the QOL scores over time and to identify factors possibly influencing QOL scores. The results suggested that MMT is effective at improving QOL scores in physical, psychological, and social domains. Being currently employed, having good family relationships, job as the source of income, and particularly a longer time in treatment were significantly associated with QOL improvements in at least one domain. The study's limitations are noted.