Objectives To evaluate performance of kidney function estimation equations and to determine the frequency of drug dose discordance in an older population. Design Cross-sectional analysis of data from community-dwelling volunteers randomly selected from the Baltimore Longitudinal Study of Aging from January 1, 2005–December 31, 2010. Subjects Two hundred sixty-nine men and women with a mean ± SD age of 81 ± 6 years, mean serum creatinine concentration (Scr) of 1.1 ± 0.4 mg/dl, and mean measured 24-hour creatinine clearance (mClcr) of 53 ± 13 ml/minute. Measurements and Main Results Kidney function was estimated by using the following equations: Cockcroft-Gault (CG), Modification of Diet in Renal Disease Study (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The performance of each equation was assessed by measuring bias and precision relative to mClcr. Dose calculation errors (discordance) were determined for 10 drugs requiring renal dosage adjustments to avoid toxicity when compared to the FDA-approved dosages. The CG equation was the least biased estimate of mClcr. The MDRD and CKD-EPI equations were significantly positively biased compared to CG (mean ± SD 34 ± 20% and 22 ± 15%, respectively, p<0.001) and mClcr (29 ± 47% and 18 ± 40%, respectively, p<0.001). Rounding low Scr values (< 1.0 mg/dl) up to an arbitrary value of 1.0 mg/dL resulted in CG values (44±10 mL/min) that were significantly lower than mClcr (56±12 mL/min, p<0.001) and CG (56±15 mL/min, p<0.001). The MDRD and CKD-EPI equations had median dose discordance rates of 28.6% and 22.9%, respectively. Conclusion The MDRD and CKD-EPI equations significantly overestimated creatinine clearance (mClcr and CG) in elderly individuals. This leads to dose calculation errors for many drugs, particularly in individuals with severe renal impairment. Thus, GFR-estimating equations should not be substituted in place of the CG equation in older adults for the purpose of renal dosage adjustments. In addition, the common practice of rounding or replacing low Scr values with an arbitrary value of 1.0 mg/dL for use in the CG equation should be avoided. Additional studies that evaluate alternative eGFR equations in the older populations that incorporate pharmacokinetic and pharmacodynamic outcomes measures are needed.