We undertook this study to prospectively evaluate whether cigarette smoking was associated with an increased risk of developing hypertension. Smoking is a well-recognized risk factor for cardiovascular disease. Few prospective cohort studies have examined the relationship between smoking and hypertension. We conducted a prospective cohort study among 28,236 women in the Women's Health Study who were initially free of hypertension, cardiovascular disease, and cancer. Detailed risk factor information, including smoking status, was collected from self-reported questionnaires. We used Cox proportional hazards survival models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension (defined as either new diagnosis, the initiation of antihypertensive medication, systolic blood pressure > or =140 mm Hg or diastolic blood pressure > or =90 mm Hg). At baseline, 51% of women were never smokers, 36% were former smokers, 5% smoked 1 to 14 cigarettes, and 8% smoked > or =15 cigarettes per day. During a median of 9.8 years, there were 8,571 (30.4%) cases of incident hypertension. The age-adjusted HRs of developing hypertension among never, former, and current smokers of 1 to 14 and > or =15 cigarettes per day were 1.00 (reference), 1.04 (95% CI 0.99 to 1.09), 1.00 (95% CI 0.90 to 1.10), and 1.10 (95% CI 1.01 to 1.19), respectively. In multivariable models further adjusting for lifestyle, clinical, and dietary variables, the corresponding HRs were 1.00 (reference), 1.03 (95% CI 0.98 to 1.08), 1.02 (95% CI 0.92 to 1.13), and 1.11 (95% CI 1.03 to 1.21), respectively. Among women who smoked > or =25 cigarettes per day, the multivariable HR was 1.21 (95% CI 1.06 to 1.39). In this large cohort of women, cigarette smoking was modestly associated with an increased risk of developing hypertension, with an effect that was strongest among women smoking at least 15 cigarettes per day.