Objective  To explore and analyze risk factors of bleeding complication of cytological biopsy of thyroid nodules under guidance of ultrasonography. Methods  A total of 402 patients（416 thyroid nodules) underwent the cytological biopsy from May 2013 to May 2015 in our hospital. Risk factors of bleeding were experience of examiners, needle size, and size, echo, vascularity, calcification, and location of nodules, and gender, age, and blood pressure of patients. Correlations between risk factors and bleeding rate were analyzed by χ2 test, Fisher P test, t test, t’ test, and multivariate logistic regression. Results  Among 416 thyroid nodules undergoing cytological biopsy, 23 of them occurred bleeding complication. The bleeding rate significantly correlated with thicker needles (P=0.005), hypervascular nodules (P=0.001), nodules under the capsule (P<0.001), and increase of systolic blood pressure (P<0.001). The bleeding rate did not significantly correlate with size, echo, and calcification of nodules, experience of examiners, and gender and age of patients. Conclusion  The bleeding complication of cytological biopsy of thyroid nodules under guidance of ultrasonography has relevant independent risk factors.