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Vanishing bile duct syndrome is a rare complication of classical Hodgkin’s lymphoma (cHL) which may present with significant cholestasis and hepatic dysfunction. Management is primarily focused on chemotherapy and symptomatic management of cholestatic liver failure. We describe a case of a man in his 60s with relapsed cHL with significant cholestatic liver injury who was treated with brentuximab vedotin complicated by renal failure. The complex decision-making surrounding chemotherapeutic choice with the presence of multiorgan dysfunction is discussed with a review of literature describing regimens in similar clinical circumstances.