Exercise capacity as measured by peak oxygen uptake (Vo 2peak ) is low in hemodialysis patients. The present study assesses determinants of VO 2peak in patients with chronic kidney failure who either changed kidney replacement modality to frequent hemodialysis therapy or received a kidney transplant.Cohort study with assessment at baseline and 6 months after modality change.Participants included nondiabetic individuals receiving conventional hemodialysis who: (1) remained on conventional hemodialysis therapy (n = 13), (2) changed to short daily hemodialysis therapy (n = 10), or (3) received a transplant (n = 5) and (4) individuals who underwent a pre-emptive transplant (n = 15). Additionally, 34 healthy controls were assessed at baseline only.Modality change.Exercise capacity, assessed using the physiologic components of the Fick equation (Vo 2 = cardiac output × a-vo 2dif , where a-vo 2dif is arterial to venous oxygen difference) was determined using measurement of Vo 2peak and cardiac output during symptom-limited exercise testing. Analysis of covariance was used to compare differences in changes in Vo 2peak , cardiac output, heart rate, stroke volume, and a-vo 2dif at peak exercise between participants who remained on hemodialysis therapy and those who underwent transplant.Transplant was the only modality change associated with a significant change in Vo 2peak , occurring as a result of increased peak cardiac output and reflecting increased heart rate without a change in peak a-vo 2dif despite increased hemoglobin levels. There were no differences in participants who changed to daily hemodialysis therapy compared with those who remained on conventional hemodialysis therapy.Small nonrandomized study.Vo 2peak increases significantly after kidney transplant, but not with daily hemodialysis; this improvement reflects increased peak cardiac output through increased peak heart rate. Despite statistical significance, the increase in Vo 2peak was not clinically significant, suggesting the need for interventions such as exercise training to increase Vo 2peak in all patients regardless of treatment modality.