Oxidative stress has been proposed as a mechanism by which the accelerated rate of cardiovascular disease (CVD) observed in maintenance hemodialysis (HD) patients may be explained. This study examined the effects of HD and CVD on serum malondialdehyde (MDA) levels as a marker of oxidative stress in HD patients with and without prevalent CVD. Serum MDA levels and CVD prevalence in HD were modeled. Serum MDA was determined using spectrophotometry in HD patients (N = 76, 53 men and 23 women, mean age 63.8 years) immediately prior to and at the conclusion of one midweek HD treatment. Traditional CVD risk factors, including serum lipids, lipoproteins, apolipoproteins, and fibrinogen, were also measured, as were serum chemistry and dialysis adequacy. Mean serum MDA levels were significantly elevated in HD patients with prevalent CVD compared with those without, whereas serum lipoprotein and plasma fibrinogen levels did not differ between the two groups. Patients in the highest compared with the lowest tertile of postdialysis MDA were nearly four times as likely to have prevalent CVD, and serum MDA was the single strongest predictor of prevalent CVD in this patient population. These findings indicate the presence of oxidative stress in HD patients, and are consistent with the theory of oxidative stress as a factor in accelerated CVD in this population.