Background: Vascular access thrombosis (VAT) is one of the most common morbidity in hemodialysis patients. The development of arteriovenous fistula thrombosis is associated with vascular intimal hyperplasia. Some studies suggested that serum C-reactive protein (CRP) predicts the development of vascular intima hyperplasia that conduces vascular access stenosis and thrombosis. This study aimed to access the clinical usefulness of CRP in predicting VAT in hemodialysis patients. Methods: We retrospectively reviewed all prevalent hemodialysis patients with native arteriovenous fistula (nAVF) between November 2001 and November 2004. The CRP levels and relation to the development of VAT was analyzed with Kaplan-Meier analysis in four groups of patients divided according to their serum CRP levels. Besides serum CRP levels, other factors possibly influencing vascular access thrombosis were also considered: gender, age, diabetes, aspirin, smoking, statin, serum albumin, hematocrit, cholesterol >200 mg/dl, Calcium-phosphate product, and intact parathyroid hormone >200 pg/ml. Results: We retrospectively reviewed 223 chronic hemodialysis patients. 198 patients with forearm nAVF and 25 with upper arm nAVF were included. Of the above 223 patients, 51 experienced one or more VAT episodes. In Kaplan-Meier survival analysis, patients with serum CRP levels >0.8 mg/dl were prone to develop VAT (log-rank, p < 0.001). In a multivariate Cox regression model, serum CRP greater than 0.8mg/dl was confirmed to be an independent predictor of VAT with a relative risk of 16.6 times (95% CI, 7.85–35.1). The area under the receiver operator characteristic (ROC) curve of CRP >0.8 mg/dl in predicting VAT events is 0.785 (95% CI, 0.712–0.858; p < 0.001). Sensitivity and specificity of CRP (>0.8 mg/dl) in predicting VAT were 80.4 and 72.7%. Conclusions: The serum CRP levels not only predict cardiovascular disease and mortality in hemodialysis patients but also predict the development of vascular access thrombosis in chronic hemodialysis patients.