This study sought to investigate the association of baseline serum cystatin C levels with myocardial perfusion and cardiac functional recovery in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). 108 patients with a first anterior STEMI who underwent PPCI were enrolled. Serum cystatin C was measured by immunoturbidimetric method. Patients were divided into two groups according to the median cystatin C levels on admission: group 1 (≥median, n = 54) and group 2 (<median, n = 54). Myocardial perfusion was assessed by angiographic criteria, ST-segment resolution, and the index of microcirculatory resistance (IMR). Echocardiographic wall motion score index was analyzed on admission and at 6-month follow-up. Patients with angiographically, electrocardiographically no-reflow had significantly higher cystatin C levels on admission. Patients with an IMR ≥33.7 U also had significantly higher cystatin C levels. The WMSI showed a greater improvement in group 2 than in group 1 and there was a significant negative correlation between improvement of WMSI and the cystatin C levels. There was no significant difference in MACEs between the 2 groups. However, congestive heart failure (CHF) was observed significantly more frequent in group 1 than in group 2 (18.5 vs. 5.6 %, p = 0.022). Multivariate logistic regression analysis demonstrated that cystatin C levels at admission were a significant independent predictor of angiographic no-reflow and the development of CHF at 6-month follow-up. Elevated cystatin C levels at admission were independently associated with impaired myocardial perfusion, poor cardiac functional recovery and development of CHF in patients with anterior STEMI undergoing PPCI.