Our aim was to compare contrast-enhanced color Doppler voiding urosonography (VUS) and direct radionuclide voiding cystography (DRVC) to determine the usefulness of ultrasonography (US) in the detection and grading of vesicoureteral reflux (VUR). In this study, the two techniques were performed simultaneously on a group of 64 children referred for the evaluation of VUR. DRVC detected VUR in 54/128 ureterorenal units, and VUS confirmed reflux in 44 (81%). Only in two cases was the reflux not confirmed by DRVC (97% specificity). Ten units with minimal grade I VUR detected by DRVC were not identified by VUS. For identification of grade II and III reflux, sensitivity of VUS reached 100%. Ten units with grade I VUR at DRVC presented grade II at VUS. Eleven units with grade II VUR at DRVC presented grade III at VUS. In conclusion, contrast-enhanced VUS is a useful diagnostic tool for the detection of VUR in children. Our data suggest a higher diagnostic accuracy of urosonography compared to radionuclide cystography in the determination of the grade of VUR; this may have significant consequences on the management of young patients affected by VUR.