We report on the use of multidetector computed tomography (MDCT) in the diagnosis of prosthetic heart valve thrombosis and a giant left atrial (LA) thrombus extending into the LA appendage (LAA), in comparison with findings of transesophageal echocardiography (TEE). A 52-year-old woman with an eight-year history of mechanical mitral valve (MMV) replacement presented with progressive dyspnea. The electrocardiogram (ECG) showed atrial fibrillation. Transesophageal echocardiography showed severely increased MMV gradients and decreased MMV area. Two thrombi were identified on the atrial aspect of the MMV, one restricting the motion of the lateral leaflet, and the other localized on the septal side of the valve ring. Two other thrombi were also visualized, one in the LA and the other in the LAA, measuring 4.3 x 1.3 cm and 2.1 x 1 cm, respectively. ECG-gated 64-slice contrast-enhanced MDCT depicted a thrombus, involving both atrial and ventricular aspects of the MMV, and also a giant thrombus, 8.3 x 2.4 cm in size, in the LA extending into the LAA. The patient underwent redo-mitral valve replacement, LA thrombectomy, and LAA ligation, and was discharged uneventfully. The size and localization of thrombi in the LA and on the explant MMV matched to the findings of MDCT. In this case, MDCT was superior to TEE in showing the precise nature of both MMV thrombosis and the integrated thrombus involving the LA and LAA.