As creatinine-based estimates of renal function are inaccurate in older adults, an alternative is an estimated glomerular filtration rate (eGFR(cys)) based on cystatin C. We examined the prospective association between chronic kidney disease (CKD(cys)) as determined by eGFR(cys) with the primary outcome of incident mobility disability and the secondary outcome of change in gait speed. Framingham Offspring Study participants older than 60 years and free of mobility disability at baseline (1998-2001) were eligible. Baseline CKD(cys) was defined as eGFR(cys) less than 60 mL/min/1.73 m(2). At follow-up (2005-2008), the outcomes of mobility disability, defined as self-reported inability to walk 1/2 mile and/or climb a flight of stairs, and gait speed were measured. Logistic and linear regression models were adjusted for age, sex, body mass index, smoking, diabetes, C reactive protein, and physical activity. Of 1,226 participants, 230 (19%) had CKD(cys) at baseline. After a mean follow-up of 6.6 years, 185 (15%) developed mobility disability. Of those with CKD(cys), 60 (26%) developed mobility disability. Those with CKD(cys) had greater odds of mobility disability in the age- and sex-adjusted (odds ratio [OR] 1.91, 95% CI 1.32, 2.75) and fully adjusted (OR 1.55, 95% CI 1.05, 2.31) models compared with those without CKD(cys). In fully adjusted models, participants with CKD(cys) had greater gait speed declines than those without CKD(cys) (β = 0.07 [SE 0.02], p = .0022). CKD(cys) was associated with higher odds of incident mobility disability and greater decline in gait speed, highlighting the loss of physical independence in elders with CKD.