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). 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. 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. 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. 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. https://doi.org/10.1289/EHP3047.