Objective To study the effect of high doses of thiamine (250 mg/day) and pyridoxine (200 mg/day) supplementation on plasma levels of advanced glycation end products and other oxidative stress markers in hemodialysis patients. Design An interventional survey. Setting This study was conducted at an outpatient nephrology clinic. Intervention and Patients We performed a randomized placebo-controlled study over 8 weeks in 50 patients (53% men, age 52.9 ± 3.4 years) on regular hemodialysis. Main Outcome Measures The patients were divided into 2 groups of 25 patients in each arm. Before starting the study, the patients in both groups were matched by age, gender, inflammatory profile (plasma interleukin [IL]-6 and high-sensitivity C-reactive protein [hsCRP]), and nutritional status (subjective global assessment and protein nitrogen appearance). Results In all, 40 of 50 patients completed the study (19 patients in the vitamin group and 21 in the placebo group). Serum albumin, plasma hsCRP, IL-6, advanced oxidation protein products, pentosidine and 8-hydroxy-2′-deoxyguanosine were measured before and after treatment in each group. In both groups, over 8 weeks of follow-up, no significant differences could be observed in oxidative stress, inflammatory, or nutritional markers. Conclusions There was no evidence showing that high doses of thiamine and pyridoxine affects oxidative stress in hemodialysis patients.