Arterio-venous fistula (AVF) failure is the most common cause of morbidity and hospitalization in hemodialysis (HD) patients. The purpose of this study is to determine the effects of smoking and blood eosinophil count on the development of AVF thrombosis in HD patients. This cross-sectional study was performed in 141 patients (M/F 80/61; age 43.4±11.6 years, HD duration 7.7±4.4 years). All of the patients; demographic features, dialysis time, smoking, medications, body mass index, co-morbid diseases and various laboratory parameters such as whole blood count and serum levels of albumin, calcium, phosphorus, uric acid, CRP, ferritin, PTH were analyzed as the possible risk factors of AVF failure. AVF thrombosis was detected in 60 patients. There was no thrombosis in 81 patients. Distributions of age, sex and HD duration were similar between both groups. Univariant analysis showed that snuff-box AVF location (p<0.0001), higher blood eosinophil count (p<0.0001), smoking (p<0.01) and higher hematocrit level (p<0.05) were all associated with AVF thrombosis. According to multivariate analysis by logistic regression model, eosinophil count (RR=1.395, p<0.005) and snuff-box location (RR=5.998, p<0.03) were predictors of AVF thrombosis. When AVF location was excluded from the analysis, smoking (RR=3.397, p<0.03) and high blood eosinophil count (RR=1.510, p<0.002) were found to be independent risk factors of thrombosis. Our study strongly indicates that smoking and high blood eosinophil count may contribute to the development of AVF thrombosis.