The purpose of this study was to assess the accuracy of Cadence Contrast Pulse Sequencing(R) (Siemens-Acuson, CA) method with injection of SonoVue(R) (Bracco Imaging SpA, Italy) for the detection and characterisation of focal liver lesions in comparison with a reference modality during routine use. Methods: 138 consecutive patients (62 women, 76 men; mean age: 52 years for women and 63 years for men) corresponding to 144 examinations with 381 lesions participated in this prospective study from December 2002 to November 2003. Inclusion criteria were lesions detected by conventional US and the availability of a reference imaging examination (CT or MR imaging) within three weeks. The underlying liver lesions characterised by a reference modality (including biopsy in 29 lesions) were distributed as follows: haemangioma (n=56), focal nodular hyperplasia (n=27), hepatocellular carcinoma (n=44), hepatocellular adenoma (n=5), liver metastasis (n=174), abscess (n=2), cysts (n=45), other benign lesions (n=24) and 3 peritoneal metastases. Results: A significant improvement was reported in the number of detected lesions between contrast-enhanced ultrasound and baseline ultrasonography (351 lesions versus 280 lesions, respectively, p<0.01), whereas no significant difference was noted between contrast-enhanced ultrasound and reference imaging (351 versus 377 lesions, respectively). On the whole, contrast-enhanced ultrasound allowed a complete diagnosis in 96% of the detected nodules with a significant improvement compared to conventional sonography in which the diagnosis was suspected in only 52% out of these cases (p<0.001). No significant difference was noted between contrast-enhanced ultrasound and the reference modality concerning characterisation of nodules. Conclusion: The present study clearly indicates that contrast-enhanced sonography using Sonovue(R) and Cadence Contrast Pulse Sequencing(R) allows real-time imaging with high accuracy and thus will be a competitive alternative to other modalities such as CT and MR imaging for liver imaging.