BACKGROUND AND OBJECTIVES: CKD is associated with poor cardiorespiratory fitness (CRF). This predefined substudy determined the effect of exercise training and lifestyle intervention on CRF and explored the effect on cardiovascular risk factors and cardiac and vascular function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between February 2008 and March 2010, 90 patients with stage 3-4 CKD were screened with an exercise stress echocardiogram before enrollment. Patients (n=83) were randomized to standard care (control) or lifestyle intervention. The lifestyle intervention included multidisciplinary care (CKD clinic), a lifestyle program, and aerobic and resistance exercise training for 12 months. CRF (peak Vo2), left ventricular function, arterial stiffness, anthropometric, and biochemical data were collected at baseline and 12 months. RESULTS: Ten percent of randomized patients had subclinical myocardial ischemia at screening and completed the study without incident. There was no baseline difference among 72 patients who completed follow-up (36 in the lifestyle intervention group and 36 in the control group). The intervention increased peak Vo2 (2.8±0.7 ml/kg per minute versus -0.3±0.9 ml/kg per minute; P=0.004). There was small weight loss (-1.8±4.2 kg versus 0.7±3.7 kg; P=0.02) but no change in BP or lipids. Diastolic function improved (increased e' of 0.75±1.16 cm/s versus -0.47±1.0 cm/s; P=0.001) but systolic function was well preserved and did not change. The change in arterial elastance was attenuated (0.11±0.76 mmHg/ml versus 0.76±0.96 mmHg/ml; P=0.01). Δ peak Vo2 was associated with group allocation and improved body composition. CONCLUSIONS: Exercise training and lifestyle intervention in patients with CKD produces improvements in CRF, body composition, and diastolic function.