OBJECTIVES: To evaluate the impact of the first selective cannabinoid type 1 (CB1) receptor blocker, rimonabant, developed for the management of cardiometabolic risk factors, on health related quality of life (HRQOL). METHODS: Over 6600 overweight/obese patients, with or without comorbidities were randomized in double-blind, placebo-controlled, 2 fixed doses (5 mg and 20 mg), parallel-group clinical trials. Patients completed the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) and the Short-Form Health Survey (SF-36) questionnaires at baseline and every 3-months up to 1 year. The IWQOL-Lite is a validated 31-item self-reported questionnaire specifically designed for HRQOL assessment in obesity and comprises 5 domains and a total score. SF-36 is a standardized generic HRQOL measure used in general population (non-specific for obesity). Analyses presented were performed on mean score changes from baseline to 1 year in the intent-to-treat population. RESULTS: At 1 year, patients administered rimonabant 20 mg once daily reported consistently greater improvement in IWQOL-Lite scores than patients in the placebo group in all domains (Physical Function, Self-esteem, Sexual Life, Public Distress, Work) and total score (p<0.001, except Work, p=0.03). SF-36 provided statistically significant results for 5/8 domains (p CONCLUSION: Using an obesity-specific questionnaire (IWQOL-Lite), rimonabant 20 mg was associated with a significant and sustained improvement in HRQOL up to 1 year. As expected, SF-36 appeared to be less sensitive to clinical changes in this overweight/obese population.