BACKGROUND: Although secondhand smoke (SHS) has been linked with various respiratory conditions and symptoms, its association with health-related quality of life (HRQOL) is unknown. METHODS: A cross-sectional study was performed of 2500 never smokers in Switzerland who participated in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults and completed a 36-Item Short Form Health Survey (SF-36) in 2002. Using linear regression models adjusting for confounders, we measured the association between HRQOL and moderate or high SHS exposure (</=3 h/d or >3 h/d) compared with no SHS exposure. Data from men and women were analyzed separately and further stratified by source of SHS (home, workplace, and public spaces). RESULTS: After adjustments, SHS was associated with reduced scores in all SF-36 domains. High SHS exposure predicted a greater reduction in HRQOL. Compared with nonexposed women, those with high SHS exposure at home had significantly lower scores on the physical functioning (-7.8, P < .001), role physical (-10.5, P = .02), bodily pain (-9.2, P = .01), and social functioning (-8.1, P = .007) domains. Exposed men had lower scores for the role physical domain (-20.0, P < .001) and a trend toward lower scores in other domains. In women, exposure to SHS at home was associated with a stronger negative effect on HRQOL than at work and in public spaces. CONCLUSIONS: Secondhand smoke is associated with reduced HRQOL, more significantly so in women. Exposure to SHS at home and high levels of exposure are associated with lower SF-36 scores, suggesting a dose-response relationship.