Introduction: Type 2 diabetes mellitus (T2DM) and hypertension (HTN) are considered strong risk factors for developing chronic kidney disease (CKD). Increased cardiorespiratory fitness (CRF) is associated with lower CKD risk. However, the CRF-CKD association in patients with T2DM and/or HTN has not been assessed.Methods: We identified 9,751 patients (age 58.6 + 10.1 years) with T2DM (N=1,444) or HTN (n=5,031) or both (n=3,276) prior to a maximal standardized exercise treadmill test (ETT) and no evidence of ischemia as indicated by the ETT. We established four CRF categories based on age-adjusted peak metabolic equivalents (METs) achieved: Least-Fit (4.6±1.2 METs; n=2,231); Low-Fit Fit (6.4±1.1 METs; n=2,693); Moderate-Fit (8.0±1.0 METs; n=2,432); and High-Fit (10.8±2.1 METs; n=2,395). We performed multivariable Cox Regression analyses to access the risk of CKD according to fitness. The models were adjusted for age, body mass index (BMI), traditional risk factors and medications. Results: During the median follow-up of 12.4 years, 1,118 patients developed CKD, accounting for 9.1 events/ 1,000 person-years of observation. The association between CRF and CKD was inverse and graded. The risk of CKD was 21% lower (Hazard Ratio [HR] 0.79; 95% confidence interval [CI] 0.77-0.81). When CRF categories were considered, the CKD risk was 44% lower for Moderate-Fit patients (HR 0.56; 95% CI 0.48-0.67) and 80% lower for High-Fit (HR 0.20; 95% CI 0.15-0.25). Similar findings were noted in patients with both T2DM and HTN. Conclusions: We noted an inverse and dose-response association between CRF and CKD incidence. The risk was attenuated significantly beyond a mean peak MET level of 8.0±1.0, suggesting that moderate increases in exercise capacity confers favorable health benefits in patients at high risk of developing CKD.