Background: Consumption of flavonoid-rich foods such as cocoa and tea may reduce cardiovascular disease risk. The flavonoids epicatechin (in cocoa and tea) and quercetin (in tea) probably play a role by reducing endothelial dysfunction and inflammation, 2 main determinants of atherosclerosis. Objective: We studied the effects of supplementation of pure epicatechin and quercetin on biomarkers of endothelial dysfunction and inflammation. Methods: Thirty-seven apparently healthy (pre)hypertensive men and women (40–80 y) participated in a randomized, double-blind, placebo-controlled crossover trial. Participants ingested (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for a period of 4 wk, in random order. Plasma biomarkers of endothelial dysfunction and inflammation were measured at the start and end of each 4-wk intervention period. The differences in changes over time between the intervention and placebo periods (¿intervention - ¿placebo) were calculated and tested with a linear mixed model for repeated measures. Results: Epicatechin changed ¿epicatechin - ¿placebo for soluble endothelial selectin (sE-selectin) by -7.7 ng/mL (95% CI: -14.5, -0.83; P = 0.03) but did not significantly change this difference (-0.30; 95% CI: -0.61, 0.01; P = 0.06) for the z score for endothelial dysfunction. Quercetin changed ¿quercetin - ¿placebo for sE-selectin by -7.4 ng/mL (95% CI: -14.3, -0.56; P = 0.03), that for IL-1ß by -0.23 pg/mL (95% CI: -0.40, -0.06; P = 0.009), and that for the z score for inflammation by -0.33 (95% CI: -0.60, -0.05; P = 0.02). Conclusions: In (pre)hypertensive men and women, epicatechin may contribute to the cardioprotective effects of cocoa and tea through improvements in endothelial function. Quercetin may contribute to the cardioprotective effects of tea possibly by improving endothelial function and reducing inflammation. This trial was registered at clinicaltrials.gov as NCT01691404.