Severe hemorrhage is the more frequent complication of thrombolysis, with intracranial bleeding the most critical one. We report a 73-year-old woman with major pulmonary embolism (PE), yet haemodynamically stable, in whom thrombolysis resulted in severe complications with acute renal failure (ARF) due to bilateral renal vein occlusion, quite unexpected; this complication has never been reported, as yet. We believe that disrupture of peripheral vein clots by thrombolysis led to migration of thrombi particles upwards to the inferior vena cava (IVC) and bilateral renal vein occlusion. However, the large thrombus straddled to the bifurcation of the main pulmonary trunk and extending to the right pulmonary artery, as visualized by transthoracic (TTE) and transesophageal echocardiogram (TEE), was not affected by thrombolysis. Finally, endogenous fibrinolytic activity, under low molecular weight heparin, resulted in a slow dissolution of the pulmonary thrombus and restoration of kidney function.