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▪ Abstract Objectives: Although long-term opioid therapy for chronic nonmalignant pain (CNMP) is widely accepted, it is controversial as to whether long-term benefits outweigh detrimental side effects. This study examines the effect of long-term opioid therapy on quality of life in terms of both physical and mental health in patients with CNMP. Methods: We retrospectively studied a cohort of patients with CNMP. With informed consent, data were collected prior to and at 6–36 months after the institution of opioid therapy in 67 patients with CNMP. The Short Form 36 (SF-36) health survey was used to compare self-reported measures of health-related quality of life in nine subscales. Visual analog scale (VAS) for pain intensity scores, disability status, and ability to return to work were also assessed. The pre- and post-therapy parameters were compared. Results: The average scores of self-reported quality of life improved significantly in eight out of the nine parameters in the SF-36 after at least 6 months of opioid therapy. The increase in reported scores was statistically significant for physical functioning, physical role, bodily pain, general health, validity, social functioning, emotional role, and mental health. No significant changes were observed in reported health transition, VAS pain scores, disability status, or return to work. Conclusions: We conclude that judicious use of opioid therapy may lead to improvement in perceived quality of life and certain aspects of functional capacity and daily activities in a highly selected group of patients with CNMP who have not responded to other therapeutic modalities for over 6 months. ▪