Contrast-enhanced voiding urosonography (VUS) is becoming more widely used for the diagnosis of vesicoureteric reflux (VUR). The purpose of this study was to evaluate the sensitivity of VUS using a second-generation ultrasound (US) contrast agent and compare it with standard fluoroscopic voiding cystourethrography (VCUG). A total of 183 children with 366 kidney-ureter units (KUUs) underwent VUS and VCUG in the same session with the same catheterization. VUS was performed after intravesical administration of 1 ml of a second-generation ultrasound contrast agent (UCA; SonoVue, Bracco, Italy). VUR was detected in 140 out of 366 cases (38%); in 89 (24.3%) by both methods, in 37 (10.1%) by VUS only, and in 14 (3.8%) by VCUG only. Although there was considerable agreement in the diagnosis of VUR by VUS and VCUG (κ=0.68, standard error [κ]=0.04), the difference in the detection rate of reflux between VUS and VCUG was significant (p<0.00001). The grade of VUR detected with VUS showed moderate agreement with grading by VCUG. Our findings suggest that contrast-enhanced harmonic VUS using a second-generation contrast agent is superior to VCUG in the detection and grading of VUR, and it should be the method of choice for this clinical indication.