Cocaine is one of the most commonly used illicit drugs. Acute renal failure is an emergent complication in patients with acute cocaine intoxication. It is well known that rhabdomyolysis and vasoconstriction can be important pathogenetic mechanisms resulting in acute renal failure in these patients. Clinically, although cocaine abuse is associated with elevated blood pressure, persistent accelerated hypertension reaching levels diagnostic of malignant hypertension is uncommon. Cocaine-induced malignant hypertension associated with morphologic features of thrombotic macroangiopathy has been rarely mentioned in the literature. We report 2 cases of cocaine abuse-associated malignant hypertension with renal failure. Kidney biopsies revealed thrombotic microangiopathy with fibrinoid necrosis of arterioles and glomerular tufts. Cocaine-mediated endothelial injury and platelet activation may play important pathogenetic roles in cocaine abusers who develop acute renal failure and malignant hypertension.