Several factors for chronic kidney disease (CKD), including diabetes, hypertension, and obesity, are described consistently in the literature; studies describing modifiable lifestyle factors, including smoking and consumption of alcohol, are sparse, sometimes contradictory. The authors examined the factors associated with CKD in a population-based cohort in Wisconsin, with emphasis on smoking and consumption of alcohol. CKD was defined as an estimated glomerular filtration rate of less than 60 ml/minute per 1.73 m(2) from serum creatinine. The authors performed two analyses: 1) cross-sectional analysis among 4,898 persons with prevalent CKD (n = 324) as the outcome of interest and 2) longitudinal analysis among 3,392 CKD-free persons at baseline, with 5-year incident CKD (n = 114) between 1993 and 1995 as the outcome of interest. Smoking and heavy drinking, defined as consumption of four or more servings of alcohol per day, were associated with CKD, independent of several important confounders. Compared with that among never smokers, the odds ratio of developing CKD was 1.12 (95% confidence interval (CI): 0.63, 2.00) among former smokers and 1.97 (95% CI: 1.15, 3.36) among current smokers. Heavy drinking was associated with CKD, with an odds ratio of 1.99 (95% CI: 0.99, 4.01). Joint exposure to both current smoking and heavy drinking was associated with almost fivefold odds of developing CKD compared with their absence (odds ratio = 4.93, 95% CI: 2.45, 9.94). Smoking and consumption of four or more servings of alcohol per day are associated with CKD.