BACKGROUND Cystatin C is a protease inhibitor that is increased in the serum of patients with chronic kidney disease (CKD) and is associated with an increased risk of developing cardiovascular disease (CVD). This study aimed to evaluate the association between serum levels of cystatin C and arterial stiffness, associated with dyslipidemia, obesity, and increased pulse pressure, in middle-aged and elderly individuals without CKD in a population in China. MATERIAL AND METHODS A cross-sectional population-based study included 1,138 patients aged ≥40 years without CKD, defined as an estimated glomerular filtration rate measured by serum creatinine (eGFRSCr) ≥60 ml/min/1.73 m². Study participants provided clinical details, including height and weight, and blood samples for serum measurements of cystatin C and lipid profiles and completed a clinical questionnaire. Pulse pressure was calculated as the mean systolic pressure (SBP) minus the diastolic pressure (DBP). Data underwent multivariate logistic regression analysis. RESULTS An increase in serum levels of cystatin C was associated with an increased risk of arterial stiffness. Each standard deviation in the increase of cystatin C resulted in a 22% increased risk of dyslipidemia, a 27% increased risk of obesity, and a 24% increased risk of increased pulse pressure, after adjusting for confounders. These associations were further confirmed in a sensitivity analysis by excluding participants with hypertension, diabetes, and patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). CONCLUSIONS In middle-aged and elderly individuals without CKD, arterial stiffness determined by obesity, dyslipidemia and increased pulse pressure, was significantly associated with increased serum levels of cystatin C.