Introduction: Particulate Matter (PM) air pollution has been associated with cardiovascular disease (CVD) in studies of long-term exposure; however, prior studies have had limited geographical variability and individual level information on prior medical history, and did not assess nonfatal events. We examined the association of long-term exposure to PM with CVD in the WHI-OS prospective cohort study. Methods: We assigned air pollution exposures to 66,801 postmenopausal US women with no history of CVD, using year 2000 averaged exposure data from the nearest representative PM sub(2.5) monitor (within 30 miles) of subject residential zipcode centroid. Monitor characteristics and annual average pollutant concentrations were obtained from EPA AirData database. Median follow-up was 6.0 years including events through August, 2003. Events were ascertained by review of hospital and medical records or death certificates with local adjudication according to standardized criteria. There were 421 fatal CVD events and 3061 incident nonfatal CVD events. Specific events included CHD death 162, cerebrovascular death 145, CVD death 114; nonfatal MI 597, angina 854, revascularization 165, coronary artery disease 148, CHF 382, stroke 570, and TIA 345. For the first incident event since enrollment, we calculated hazard ratios per 10 mu g/m super(3) increment of annual average PM sub(2.5) exposure using Cox proportional hazards regression, adjusting for age, smoking status, years smoked, cigarettes/day, diabetes, hypertension, systolic and diastolic blood pressure, BMI, and elevated cholesterol. Results: After adjustment for confounding factors, each 10 mu g/m super(3) of PM sub(2.5) was associated with a 17% increased risk of incident nonfatal and fatal CVD events, relative hazard (RH) 1.17 (95% CI: 1.06, 1.28). Risk was increased by 14% for incident nonfatal CVD events (RH 1.14; 95% CI 1.03, 1.26) and by 32% for fatal CVD events (RH 1.32; 95% CI: 1.01, 1.73). Further adjustment for second-hand smoke, occupation, SES, diet, exercise and medications did not appreciably change estimates. Discussion: Our results suggest that long-term exposure to PM sub(2.5) is associated with both CVD mortality and with nonfatal CVD events. Chronic air pollution exposure may influence CVD incidence in postmenopausal women.