Background: High density lipoprotein cholesterol concentration (HDL-C) is an established atheroprotective marker, in particular for coronary artery disease; however, HDL particle concentration (HDL-P) may better predict risk. The associations of HDL-C and HDL-P with ischemic stroke and with myocardial infarction (MI) among women and Blacks has not been well studied. We hypothesized that HDL-P would be consistently associated with MI and stroke among women and Blacks compared with HDL-C. Methods: We analyzed individual level participant data in a pooled cohort of four large population studies without baseline atherosclerotic cardiovascular disease (ASCVD) - the Dallas Heart Study (DHS) (n=2,535), Atherosclerotic Risk in Communities (ARIC) Study (n=1,595), Multi Ethnic Study of Atherosclerosis (MESA) (n=6,632) and Prevention of Renal and Vascular Endstage Disease (PREVEND) (n=5,022). HDL markers were analyzed in adjusted Cox proportional hazard models for MI and ischemic stroke. Results: In the overall population (n=15,784), HDL-P was inversely associated with the combined outcome of MI and ischemic stroke, adjusted for cardiometabolic risk factors, [hazard ratio (HR) for Q4 vs Q1 0.64, 95% confidence interval [CI] 0.52 to 0.78] as was HDL-C (HR for Q4 vs Q1: 0.76, 95% CI 0.61 to 0.94). Adjustment for HDL-C did not attenuate the inverse relationship between HDL-P and ASCVD, while adjustment for HDL-P attenuated all associations between HDL-C and events. HDL-P was inversely associated with the individual endpoints of MI and ischemic stroke in the overall population, including in women. HDL-P was inversely associated with MI among White participants but not among Black participants (HR Q4 vs Q1 for White 0.49, 95%CI 0.35-0.69; for Black 1.22, 95%CI 0.76-1.98; p interaction = 0.001). Similarly, HDL-C was inversely associated with MI among White participants (HR Q4 vs Q1 0.53, 95%CI 0.36-0.78) but had a weak direct association with MI among Black participants (HR Q4 vs Q1 1.75, 95%CI 1.08-2.83; p interaction < 0.0001). Conclusions: In comparison to HDL-C, HDL-P was consistently associated with MI and ischemic stroke in the overall population. Differential associations of both HDL-C and HDL-P for MI by Black ethnicity suggest that ASCVD risk may differ by vascular domain and ethnicity. Future studies should examine individual outcomes separately.