© 2015 National Kidney Foundation, Inc. Background Health care claims data may provide a cost-efficient approach for studying chronic kidney disease (CKD). Study Design Prospective cohort study. Setting & Participants We compared characteristics and outcomes for individuals with CKD defined using laboratory measurements versus claims data from 6,982 REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study participants who had Medicare fee-for-service coverage. Predictors Presence of CKD as defined by both the REGARDS Study (CKDREGARDS) and Medicare data (CKDMedicare), presence of CKDREGARDS but not CKDMedicare, and presence of CKDMedicare but not CKDREGARDS, and absence of both CKDREGARDS and CKDMedicare. Outcomes Mortality and incident end-stage renal disease (ESRD). Measurements The research study definition of CKD (CKDREGARDS) included estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or albumin-creatinine ratio > 30 mg/g at the REGARDS Study visit. CKD in Medicare (CKDMedicare) was identified during the 2 years before each participant's REGARDS visit using a claims-based algorithm. Results Overall, 32% of participants had CKDREGARDS and 6% had CKDMedicare. Sensitivity, specificity, and positive and negative predictive values of CKDMedicare for identifying CKDREGARDS were 15.5% (95% CI, 14.0%-17.1%), 97.7% (95% CI, 97.2%-98.1%), 75.6% (95% CI, 71.4%-79.5%), and 71.5% (95% CI, 70.4%-72.6%), respectively. Mortality and ESRD incidence rates, expressed per 1,000 person-years, were higher for participants with versus without CKDMedicare (mortality: 72.5 [95% CI, 61.3-83.7] vs 33.3 [95% CI, 31.5-35.2]; ESRD: 16.4 [95% CI, 11.2-21.6] vs 1.3 [95% CI, 0.9-1.6]) and with versus without CKDREGARDS (mortality: 59.9 [95% CI, 55.4-64.4] vs 25.5 [95% CI, 23.6-27.4]; ESRD: 6.8 [95% CI, 5.4-8.3] vs 0.1 [95% CI, 0.0-0.3]). Among participants with CKDREGARDS, those with abdominal obesity, diabetes, anemia, lower eGFR, more outpatient visits, hospitalization, and a nephrologist visit in the 2 years before their REGARDS visit were more likely to have CKDMedicare. Limitations CKDREGARDS relied on eGFR and albuminuria assessed at a single visit. Conclusions CKD, whether defined in claims or through research study measurements, was associated with increased mortality and ESRD. However, individuals with CKD identified in claims may represent a select high-risk population.