Cardiovascular (CV) disease is the most common cause of mortality in end-stage kidney disease (ESKD), and arterial stiffness, measured by pulse wave velocity (PWV), is an independent predictor of all-cause and CV mortality. B-type natriuretic peptide (BNP) levels are high in patients with CV disease and ESKD, and increases in BNP may also be a marker of CV risk. Regular exercise has many benefits on quality of life and physical strength and may also improve CV risk, but few studies have addressed the impact of exercise on CV risk in ESKD. We performed a prospective cross-over trial in 19 hemodialysis (HD) patients to assess the impact of regular exercise on surrogate markers of CV risk-arterial compliance and BNP levels. Exercise involved the use of a bicycle ergometer for minimum 30 min at each HD session for 3 months, with a 1-month washout period. Group A (n=9) exercised for the first 3 months only, while group B (n=10) performed no intradialytic exercise initially and exercised for 3 months at cross-over (month 4). Pulse wave velocity was performed using a SphygmoCor device, with concurrent measurements of BNP and other serum markers, at the commencement of the study, at 3 months, and on completion. The mean PWV (A: 10.4+/-3.1 m/s, B: 9.8+/-3.8 at baseline) showed a trend toward improvement with exercise (A: 8.7+/-2.7, p=0.07), and no significant change without (B: 10.5+/-3.6, p=0.31). After cross-over, there was an increase in PWV in group A with cessation of exercise (9.75+/-2.4, p=0.01 vs. 3 months) and an improvement in group B with exercise (9.33+/-2.3, p=0.11 vs. 3 months). When comparing PWV after 3 months of exercise vs. 3 months of no exercise (paired t test), there was a significant difference in favor of exercise (9.04+/-0.59 vs. 10.16+/-0.74, p=0.008). The mean BNP levels following 3 months of exercise were also lower than those after 3 months of no exercise (504.4+/-101.2 vs. 809.4+/-196.1[N<100], p=0.047). There was an overall improvement in PWV, and to a lesser extent BNP levels, with 3 months of intradialytic exercise compared with no exercise, suggesting that regular exercise in ESKD may be associated with improvements in arterial compliance and a reduction in CV risk.