Background: Biological mechanisms underlying fibric acid (PPARa ligand) and angiotensin II type 1 receptor blocker therapies differ. Experimental studies demonstrated cross-talking between PPARa and RAS system. We investigated vascular and metabolic responses to these therapies either alone or in combination in hypertriglyceridemic, hypertensive patients. Methods: This was a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Forty-four patients were given fenofibrate 200 mg and placebo, fenofibrate 200 mg and candesartan 16 mg, or candesartan 16 mg and placebo daily during each 2 month treatment period. Results: Fenofibrate, combined therapy, or candesartan significantly reduced systolic and diastolic blood pressure after 2 months administration compared with baseline. However, combined therapy significantly reduced blood pressure more than fenofibrate or candesartan alone (P<0.001 by ANOVA). When compared with candesartan, fenofibrate or combined therapy significantly improved the lipoprotein profile. All three treatment arms significantly improved flow-mediated dilator response to hyperemia. Combined therapy significantly decreased plasma malondialdehyde (MDA), hsCRP, and soluble CD40L levels relative to baseline measurements. Importantly, these parameters were changed to a greater extent with combined therapy when compared with monotherapy (P<0.001, P=0.002, P=0.050, and P=0.032 by ANOVA, respectively). Fenofibrate, combined therapy, and candesartan significantly increased plasma adiponectin levels and insulin sensitivity (determined by QUICKI) relative to baseline measurements. However, the magnitude of these increases were not significantly different among three therapies (P=0.246 and P=0.153 by ANOVA, respectively). Conclusions: Fenofibrate combined with candesartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypertriglyceridemic, hypertensive patients.