Background: The basic studies have demonstrated that microRNA-204 (miRNA-204) was involved in the process of atherosclerosis and vascular calcification. However, the value of miRNA-204 as a predictive biomarker for cardiovascular disease (CVD) is still controversial. The purpose of the present study was to evaluate the association between circulating miRNA-204 level and the 10-year cardiovascular disease risk score, Framingham risk score (FRS).Method: The subjects consecutively enrolled 194 patients with type 2 diabetes mellitus without cardiovascular disease at Anzhen Hospital from January 2015 to September 2016. We used the Framingham Risk Score (FRS) to evaluate the risk of cardiovascular disease. Circulating miRNA-204 levels were measured by quantitative Real-Time polymerase chain reaction (qRT-PCR).Result: The circulating miRNA-204 levels were significantly lower in high risk group of CVD (FRS > 20%) of patients (0.49 ± 0.13) compared with that in low risk group (FRS < 10%) and intermediate risk group (FRS = 10%-20%) (0.87 ± 0.19, 0.75 ± 0.25, Respectively, p < 0.001). FRS was negatively correlated with miR-204 levels (r=-0.421, p < 0.001). According to multivariate logistic analyses, miRNA-204 levels were still significantly and independently associated with the high risk of CVD after adjusting the conventional risk factor. Receiver-operating characteristic curve (ROC) analysis also showed that circulating miRNA-204 level can predict the high risk of CVD, and the specificity was higher than traditional risk factors SBP and protective factor HDL-C of CVD.Conclusion: Our study demonstrated that patients with lower circulating miRNA-204 levels were at a high risk for the progression of CVD. After adjustment for potential confounders, miRNA-204 was independently associated with CVD in patients with T2DM.