OBJECTIVE: To study the effect of a short-term yoga-based lifestyle intervention on health-related quality of life (HRQOL) in overweight and obese persons. DESIGN AND SETTING: Nonrandomized, single-arm interventional study conducted from August 2012 to March 2015 at Integral Health Clinic, Department of Physiology, All India Institute of Medical Sciences, New Delhi, India. PARTICIPANTS: Overweight (body-mass index [BMI], 23-24.9 kg/m(2)) and obese (BMI, ≥25 kg/m(2)) persons (n = 279) aged 20-60 years. INTERVENTION: Pretested yoga-based lifestyle intervention, including asanas (postures), pranayama (breathing exercises), relaxation techniques, lectures, group support, nutrition awareness program, and individualized advice. OUTCOME MEASURES: Primary outcome measure was HRQOL, measured by using short version of World Health Organization Quality of Life (WHOQOL-BREF) questionnaire. Secondary outcome measures were anthropometric variables, systolic and diastolic blood pressure, pulse rate, lipid profile, and fasting glucose. A subgroup analysis according to sex was also performed. RESULTS: The overall quality of life and health improved after short-term yoga-based lifestyle intervention in overweight and obese persons. Physical, psychological and environmental domain scores significantly increased from baseline to day 10, and efficacy was noted in both male and female subgroups. After 10 days of intervention, the following also decreased significantly: body weight, BMI, total body fat, waist and hip circumference, waist-to-hip ratio, systolic and diastolic blood pressure, total cholesterol, low-density lipoprotein, triglycerides, and fasting glucose. CONCLUSION: A short-term yoga-based lifestyle intervention had a positive effect on HRQOL in overweight and obese persons.