Renal dysfunction is a strong independent predictor of stent thrombosis. The aim of the present study was to evaluate the strength and direction of the association between kidney function and clopidogrel efficacy. The study group consisted of consecutive patients (n = 275) who underwent stent implantation. Drug efficacy was measured using the vasodilator-stimulated phosphoprotein (VASP) index 20 ± 4 hours after clopidogrel 600 mg. Nonresponse was defined as an VASP index ≥50%. Renal function was determined using serum cystatin C. The upper reference levels are 1.12 mg/L for ≤65 years of age and 1.21 mg/L for >65 years of age. Estimated glomerular filtration was calculated using cystatin C. The median value of cystatin C was 1.16 mg/L (twenty-fifth and seventy-fifth percentiles 0.96 and 1.43); 47.63% of the study population had cystatin C above reference levels and 33.1% of patients were nonresponders to clopidogrel. No correlation was found between clopidogrel efficacy assessed with the VASP index and kidney function assessed with cystatin C (Spearman r = −0.070, p = 0.248). Based on cystatin C the proportion of nonresponders to clopidogrel was 34.4% versus 31.9% (p = 0.702) in patients with impaired renal function compared to normal renal function, respectively. The proportion of clopidogrel nonresponders did not differ (p = 0.902) among groups with normal (28.8%), mildly impaired (34.8%), moderately impaired (32.9%), and severely impaired (34.8%) renal function. In conclusion, renal function assessed by cystatin C does not predict clopidogrel efficacy. Renal dysfunction is a complex entity and its significant relation to stent thrombosis cannot be explained simply by a decrease in clopidogrel efficacy.