Malignant external otitis (MEO) is a devastating external auditory canal infection usually occurring in the elderly with diabetes. MEO often progresses to potentially lethal skull base osteomyelitis (SBO) complications such as meningitis or multiple cranial nerve palsies. Poor vascularity in affected tissue due to diabetic microangiopathy and Pseudomonal infection is thought responsible for refractory infection. We conducted intraarterial antibiotic infusion (IA) in the external carotid artery of two subjects with intractable MEO deteriorating after long-term intravenous antibiotic administration with surgical debridement. IA raised the antibiotic concentration in infectious tissue. Clinical MEO manifestation was relieved just after starting IA, and IA therapy was followed by additional long-term intravenous and oral antibiotic administration, dramatically improving MEO while leaving only minimal infection at the skull base. These results demonstrate IA effectiveness in treating refractory MEO.