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Background: Enhanced external counterpulsation (EECP) enhances coronary perfusion and reduces left ventricular afterload. However, the role of EECP on renal function in cardiac patients is unknown. Our aim was to assess renal function determined by serum cystatin C in cardiac patients before and after EECP treatment., Methods: A prospective observational longitudinal study was conducted in order to evaluate renal function using serum cystatin C (Cys C) and estimated glomerular filtration rate (GFR) after 35 sessions of EECP treatment in 30 patients with chronic stable angina and/or heart failure. The median (IQR) time for follow-up period after starting EECP treatment was 16 (10-24) months., Results: Cys C significantly declined from 1.00 (0.78-1.31) to 0.94 (0.77-1.27) mg/L (p < 0.001) and estimated GFR increased from 70.47 (43.88-89.41) to 76.27 (49.02-91.46) mL/min/1.73 m(2) (p = 0.006) after EECP treatment. Subgroup analysis showed that patients with baseline GFR <60 mL/min/1.73 m(2) or NT-proBNP >125 pg/mL had a significant decrease in Cys C when compared to other groups (p < 0.01)., Conclusions: The study demonstrated that EECP could improve long-term renal function in cardiac patients especially in cases with declined renal function or with high NT-proBNP., Trial Registration: The study was registered in the clinical trial as International Standard Randomized Controlled Trial Number ISRCTN11560035.