BACKGROUND: There is growing evidence that exposure to ultrafine particles (UFP; particles smaller than [Formula: see text]) 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 [Formula: see text] ([Formula: see text]), PM with aerodynamic diameter [Formula: see text] ([Formula: see text]), and [Formula: see text]. RESULTS: Long-term UFP exposure was associated with an increased risk for all incident CVD [[Formula: see text] per [Formula: see text]; 95% confidence interval (CI): 1.03, 1.34], myocardial infarction (MI) ([Formula: see text]; 95% CI: 1.00, 1.79), and heart failure ([Formula: see text]; 95% CI: 1.17, 2.66). Positive associations were also estimated for [Formula: see text] ([Formula: see text]; 95% CI: 1.01, 1.48 per [Formula: see text]) and coarse PM ([Formula: see text]; HR for all [Formula: see text]; 95% CI: 1.01, 1.45 per [Formula: see text]). CVD was not positively associated with [Formula: see text] (HR for all [Formula: see text]; 95% CI: 0.75, 1.28 per [Formula: see text]). HRs for UFP and CVAs were positive, but not significant. In two-pollutant models ([Formula: see text] and [Formula: see text]), positive associations tended to remain for UFP, while HRs for [Formula: see text] and [Formula: see text] generally attenuated towards the null. CONCLUSIONS: These ...