OBJECTIVES: The purpose of this study was to examine the extent to which reported quality of life differs between smokers and nonsmokers when other physical and mental health status factors are controlled for. METHODS: Data from the 2003 Medical Expenditure Panel Survey was used. This dataset represents 290,604,436 non-institutionalized adults in the US, 22% of which were smokers. Three initial logistic regressions were run using smoking status as the dependent variable. The first logistic regression included demographics and education level as explanatory variables; the second model included diagnosis-related variables; and the last model considered other health-related issues such as feeling calm and peaceful, having functional limitations, etc. Variables significantly associated with smoking in the logistic regressions were used as covariates in a linear regression with perceived health status as the dependent variable. A univariate model estimating the effect of smoking on health status was also run. RESULTS: After adjusting for demographics and other health status measures, smoking remained a highly significant factor affecting perceived health status, although the influence of smoking decreased by 40%. In the univariate model, the coefficient on smoking was -0.43 (t=-15.23, p<0.001). When other explanatory variables were included in the model, the coefficient on smoking status was -0.26 (t=-11.00, p<0.001). In the final model, all explanatory variables showed a significant effect on perceived health status, except for sex. Factors with the highest effect on health status (largest absolute t-statistics) were pain, any physical limitation, high blood pressure, and smoking, respectively. CONCLUSIONS: Although the outcome variable is measured on a five-point scale, from 1 (“excellent”) to 5 (“poor”), performing an exploratory generalized ordered logit model suggested similar associations. The effect of smoking was consistent throughout the scale of health status ratings.