The effect of olmesartan, an inverse angiotensin II type 1 receptor blocker (ARB), on oxidative stress in hemodialysis (HD) patients is not fully understood, and has not been widely investigated in vitro or in vivo. We determined the amount of oxidized albumin and albumin hydroperoxides formed during incubation in the absence and presence of olmesartan by high-performance liquid chromatography (HPLC) and by a ferrous oxidation xylenol assay in an in vitro study. Six hypertensive HD patients were treated with 40 mg of olmesartan once daily, and blood pressure monitoring (BPM) was performed after 0, 4, and 8 weeks of treatment. The ratio of oxidized to unoxidized albumin was also determined. The oxidized albumin ratios and levels of albumin hydroperoxides were significantly decreased in a concentration-dependent manner in the presence of olmesartan, compared with the absence of olmesartan (p<0.05) in in vitro studies. In HD patients, olmesartan also significantly reduced systolic and diastolic blood pressure after 4 weeks, with a further significant decrease after 8 weeks. The ratio of oxidized to unoxidized albumin was markedly decreased after 4 weeks and these lower levels were maintained at 8 weeks. Olmesartan effectively lowered the extent of oxidation of albumin in both in vitro and in vivo studies, and this effect might confer benefits beyond a reduction in blood pressure.