Chronic kidney disease (CKD) is an increasing cause of morbidity and mortality in the United States. Prospective data on risk factors for CKD are limited to men, and few studies examine the importance of smoking. The authors performed a community-based, prospective observational study of 20-yr duration to examine the association between hypertension and smoking on the future risk of CKD in 23,534 men and women in Washington County, Maryland. CKD was identified as end-stage renal disease in the Health Care Financing Administration database or kidney disease listed on the death certificate. All cases were confirmed as CKD by medical chart review. Adjusted relative hazards of CKD were modeled using Cox proportional hazards regression including age as the time variable and baseline BP, cigarette smoking, gender, and diabetes status as risk factors. The adjusted hazard ratio (95% confidence interval) of developing CKD among women was 2.5 (0.05 to 12.0) for normal BP, 3.0 (0.6 to 14.4) for high-normal BP, 3.8 (0.8 to 17.2) for stage 1 hypertension, 6.3 (1.3 to 29.0) for stage 2 hypertension, and 8.8 (1.8 to 43.0) for stages 3 or 4 hypertension compared with individuals with optimal BP. In men, the relationship was similar but somewhat weaker than in women, with corresponding hazard ratios of 1.4 (0.2 to 12.1), 3.3 (0.4 to 25.6), 3.0 (0.4 to 22.2), 5.7 (0.8 to 43.0), and 9.7 (1.2 to 75.6), respectively. Current cigarette smoking was also significantly associated with risk of CKD in both men and women (hazard ratio in women 2.9 [1.7 to 5.0] and in men 2.4 [1.5 to 4.0]). A large proportion of the attributable risk of CKD in this population was associated with stage 1 hypertension (23%) and cigarette smoking (31%). In conclusion, CKD risk shows strong graded relationships to the sixth report of the Joint National Committee (JNC-VI) on Prevention, Detection Evaluation and Treatment of High BP criteria for BP, to diabetes, and to current cigarette smoking that are at least as strong in women as in men.