<b><i>Background/Aims: </i></b>The relationship between carotid artery plaque burden, phenotype and serum cystatin C at normal and impaired renal function is still unclear.<b><i> Methods: </i></b>Demographic characteristics, carotid ultrasonography and other relevant information of 1,477 patients were collected. The association of carotid artery plaque burden, plaque phenotype with serum cystatin C was evaluated by strategy analysis based on renal function.<b><i> Results: </i></b>Serum cystatin C (<i>OR</i>=2.05, 95% CI: 1.83-2.29, <i>P</i><.01) was a risk factor of stable plaque among patients with normal glomerular filtration rate. However, in the patients with mild impaired renal function, serum cystatin C was not only a risk factor for stable plaque (<i>OR</i>=1.60, 95%CI: 1.43-1.78,<i> P</i><.001) but also was a risk factor for unstable plaque (<i>OR</i>=1.21, 95%CI: 1.10-1.32, <i>P</i><.001). The smoothing function curve and a three-piecewise linear regression revealed that a nonlinear relationship was observed between serum cystatin C and plaque burden. When serum cystatin C was in the range of 0.75-1.30 (mg/L), the plaque burden tended to increase.<b><i> Conclusion: </i></b>In normal renal function, serum cystatin C may confer stability of plaques. In mildly impaired renal function, serum cystatin C is a risk predictor of plaques. In normal renal function circumstances, serum cystatin C may benefit to the stability of plaques. In mild impaired renal function circumstances, serum cystatin C are a risk predictors of plaques.