Contrast-enhanced ultrasound (CEUS) can be used to evaluate microcirculation in cancers, which in turn is associated with the biologic features and ultimately patient prognosis. We conducted a retrospective analysis to examine potential association between CEUS parameters and prognosis in patients with papillary thyroid cancer (PTC). The analysis included 306 patients who underwent CEUS prior to thyroidectomy at our center during a period from 2012 to 2019. Subjects with excellent response (ER) were compared to the non-ER group (including indeterminate response, biochemical incomplete response and structural incomplete response). During the median follow-up of 34 months, ER was observed in 195 (63.7%) subjects. The remaining 111 (36.3%) patients developed non-ER events, with distant metastasis in five (1.6%) cases. In a multivariate COX regression, non-ER event was associated with the male sex (OR = 1.83, 95%CI: 1.21-2.76) and blood-rich enhancement in CEUS (OR = 1.69, 95%CI: 1.04-2.75). Based on this finding, we developed a predictive model: high risk for developing non-ER events was defined as having both risk factors; low risk was defined as having none or only one risk. In receiver operating characteristic (ROC) analysis, the area under the curve was 0.59 (95%CI: 0.52-0.66). The sensitivity and specificity were 17.1 and 95.4%, respectively. The positive and negative predictive values were 67.9 and 66.9%, respectively. In conclusion, blood-rich enhancement in CEUS is associated with non-ER events after thyroidectomy in patients with PTC.