Despite the fact that the serum creatinine level is notoriously unreliable for the estimation of glomerular filtration rate (GFR) in the elderly, the serum creatinine concentration and serum creatinine-based formulas, such as the Modification of Diet in Renal Disease study equation (MDRD) are the most commonly used markers to estimate GFR. Recently, serum cystatin C-based formulas, the newer creatinine formula (the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI creatinine formula), and an equation that uses both serum creatinine and cystatin C (CKD-EPI creatinine and cystatin formula) were proposed as new GFR markers. The aim of our study was to compare the MDRD formula, CKD-EPI creatinine formula, CKD-EPI creatinine and cystatin formula, and simple cystatin C formula (100/serum cystatin C) against 51Cr-EDTA clearance in the elderly. A total of 317 adult Caucasian patients aged >65 years were enrolled. In each patient, 51Cr-EDTA clearance, serum creatinine, and serum cystatin C were determined, and the GFR was calculated using the MDRD formula, CKD-EPI formulas, and simple cystatin C formula. Statistically significant correlations between 51Cr-EDTA clearance and all formulas were found. In the receiver operating characteristic (ROC) curve analysis with a cut-off of GFR 45 mL/min/1.73 m2, a higher diagnostic accuracy was achieved with the equation that uses both serum creatinine and cystatin C (CKD-EPI creatinine and cystatin formula) than the MDRD formula (P < 0.013) or CKD-EPI creatinine formula (P < 0.01), but it was not higher than that achieved for the simple cystatin C formula (P = 0.335). Bland and Altman analysis for the same cut-off value showed that the creatinine formulas underestimated and the simple cystatin C formula overestimated measured GFR. All equations lacked precision. The accuracy within 30% of estimated 51Cr-EDTA clearance values differ according to the stage of CKD. Analysis of the ability to correctly predict GFR below and above 45 mL/min/1.73 m2 showed a high prediction for all formulas. Our results indicate that the simple cystatin C formula, which requires just one variable (serum cystatin C concentration), is a reliable marker of GFR in the elderly and comparable to the creatinine formulas, including the CKD-EPI formulas.