Intentional iron overdose in adults is uncommon. Clinical consequences are variable and depend on the quantity of iron ingested and the delay to treatment. Severe iron overdose can lead to multi-organ failure and acute hepatic necrosis. Here, we report three cases of polypharmacy overdose including iron resulting in acute liver failure. Despite maximum supportive care including liver transplantation in two cases, all patients died. Iron poisoning may have an additive toxic effect in drug-induced acute liver failure and worsen outcome.