OBJECTIVE: We conducted a prospective study to compare sonography, color Doppler sonography, and contrast-enhanced sonography for the detection and characterization of portal and hepatic vein thrombosis complicating hepatic malignancies. SUBJECTS AND METHODS: Three hundred sixteen patients with biopsy-proved hepatic tumors were studied at baseline and 3 months later with sonography, color Doppler sonography, and contrast-enhanced sonography. Thrombosis was defined as the presence of intraluminal echogenic material at sonography, absence of intraluminal color signals at color Doppler sonography, and presence of nonenhancing intraluminal area at contrast-enhanced sonography. Thrombi were considered malignant if they displayed continuity with tumor tissue at sonography, intrathrombus color signals at color Doppler sonography, and enhancing signals at contrast-enhanced sonography, both having arterial waveforms at Doppler spectral examination. Definitive diagnoses were obtained by sonographically guided biopsy except for thrombi displaying at conventional sonography unequivocal continuity with tumor tissue. RESULTS: Thrombosis was detected in 79 (25.0%) of 316 patients at baseline and in 83 (26.3%) of 316 patients after 3 months. Eighty-one (97.6%) of the 83 thrombi were malignant. Definitive diagnosis was performed by imaging in 60 (72.3%) of the 83 cases and by biopsy in 23 cases (27.7%). For thrombus detection, contrast-enhanced sonography displayed significantly higher sensitivity than color Doppler sonography (p = 0.004) and borderline superiority over sonography (p = 0.058). For thrombus characterization, contrast-enhanced sonography was significantly more sensitive than color Doppler sonography (p < 0.0005) and conventional sonography (p = 0.02). CONCLUSION: Contrast-enhanced sonography is superior to sonography and color Doppler sonography for the detection and characterization of portal and hepatic vein thrombosis complicating hepatic malignancies.