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Introduction: The quality of life (QOL) of substance users is known to be impaired. Sudarshan Kriya Yoga (SKY), a yogic breathing program has potential to improve QOL and needs evaluation in an Indian setting. Aims: Study aimed to assess changes in QOL in treatment seeking male opioid dependent users following practice of SKY program. Settings and Design: Users were randomized into study (n = 55) and control group (n = 29). Study group besides standard treatment (long term pharmacotherapy with buprenorphine in flexible dosing schedule) underwent a 3 days, 12 h SKY program while control group received standard treatment alone. Materials and Methods: World Health Organization QOL-brief scale was used to measure QOL and urine tested to assess recent drug use. Assessments were made at baseline and at 3 and 6 months. Statistical Analysis: Data were analyzed using generalized estimation equation to assess within group change with time and the overall difference between groups for changes at assessment points.Results: Overtime within study group, all four QOL domain scores were significantly higher at 6 months. Between group comparison showed significant increase in physical (P < 0.05); psychological (P < 0.001) and environment domains (P < 0.001) for study group while control group showed significant changes in social relationship domain only. Urine screening results were negative for study group indicating no drug use at 6 months. Conclusion: SKY as a complementary therapy was found beneficial in improving QOL for group practicing it and is recommended for use as low cost and low-risk adjunct in substance treatment settings in India.