Inadvertent intra-arterial drug injection occurs rarely, but it can cause very serious clinical complications, and thus, awareness of inadvertent intra-arterial drug injection is needed. The complications mainly result from iatrogenic reasons and can occur because of vascular variations in the arteries, under circumstances where normal intravenous injection is difficult, or in drug abusers who perform self-injection. The adverse effect associated with intra-arterial drug injection is serious and may lead to necrosis, requiring amputation of the affected extremity, infection, pseudoaneurysm, rhabdomyolysis, compartment syndrome, and permanent disability. However, the etiology of such adverse effects has not been clearly identified and treatment methods have not yet been established. We encountered a patient who developed necrosis of the thumb after an inadvertent injection of diclofenac sodium in the radial artery due to variations in the forearm arteries. Here, we report the prevention and treatment of, and precautions against, the dangers of intra-arterial drug injection.