BACKGROUND: There is growing evidence that exposure to ultrafine particles (UFP; particles smaller than 100 nm) may play an underexplored role in the etiology of several illnesses, including cardiovascular disease (CVD). OBJECTIVES: We aimed o investigate the relationship between long-term exposure to ambient UFP and incident cardiovascular and cerebrovascular disease (CVA). As a secondary objective, we sought to compare effect estimates for UFP with those derived for other air pollutants, including estimates from two-pollutant models. METHODS: Using a prospective cohort of 33,831 Dutch residents, we studied the association between long-term exposure to UFP (predicted via land use regression) and incident disease using Cox proportional hazard models. Hazard ratios (HR) for UFP were compared to HRs for more routinely monitored air pollutants, including particulate matter with aerodynamic diameter ≤10 lm (PM10), PM with aerodynamic diameter ≤2:5 (PM2:5), and NO2. RESULTS: Long-term UFP exposure was associated with an increased risk for all incident CVD [HR = 1:18 per 10,000 particles=cm3; 95% confidence interval (CI): 1.03, 1.34], myocardial infarction (MI) (HR = 1:34; 95% CI: 1.00, 1.79), and heart failure (HR = 1:76; 95% CI: 1.17, 2.66). Positive associations were also estimated for NO2 (HR for heart failure = 1:22; 95% CI: 1.01, 1.48 per 20 lg=m3) and coarse PM (PMcOarse; HR for all CVD = 1:21; 95% CI: 1.01, 1.45 per 10 lg=m3). CVD was not positively associated with PM2:5 (HR for all CVD = 0:95; 95% CI: 0.75, 1.28 per 5 lg=m3). HRs for UFP and CVAs were positive, but not significant. In two-pollutant models (UFP + NO2 and UFP + PMcOarse), positive associations tended to remain for UFP, while HRs for PMcOarse and NO2 generally attenuated towards the null. CONCLUSIONS: These findings strengthen the evidence that UFP exposure plays an important role in cardiovascular health and that risks of ambient air pollution may have been underestimated based on conventional air pollution metrics.