A 10-year-old boy who had had a splenectomy for his underlying β-thalassemia was admitted to the Chiang Mai University (CMU) Hospital for a gangrenous ulcer on his right leg and claudication. Six weeks prior to admission, he first noticed a small pustular lesion on his right ankle which later spontaneously ruptured and became an ulcer. There was no previous history of trauma. The patient reported frequently working in a rice field with his parents. He was brought to a local hospital where the diagnosis of pyomyositis was made. Incision and drainage were performed and his symptoms improved. Two weeks prior to admission another pustular lesion developed on his right shin which finally became a gangrenous ulcer. His other symptoms were fever, severe resting pain, intermittent claudication and swollen right knee. He was transferred to a district hospital where an ultrasound showed thrombosis of the right femoral and popliteal artery and enlarged lymph nodes at the right popliteal fossa. Arthrocentesis of the right knee revealed 855,000 cells/mm3 of WBC (polymorphonuclear cell 74%, mononuclear cell 26%). He was diagnosed as having septic arthritis. Intravenous cloxacillin was given and the patient was transferred to the CMU Hospital. Physical examination at the CMU Hospital revealed old ulcerated scars on the right shin and ankle, marked tenderness along the right leg, cool skin, diminished pulses of the right femoral and popliteal arteries, and absence of pulses of the right posterior tibialis and dorsalis pedis arteries. Computerized tomography angiography (CTA) showed occlusion of the lower third of the right external iliac artery, as well as the right common femoral, superficial femoral, popliteal, anterior tibial, tibioperonial, peroneal and dorsalis pedis arteries. Multiple collateral vessels were seen around the right knee. He was diagnosed as a case of vascular pythiosis and had a high-above-knee amputation of his right leg. Antibody to P. insidiosum was detected in a serum sample by immunoblot and immunochromatography tests (ICT). Fungal culture followed by nucleic sequence analysis of 18S rRNA [] was positive for P. insidiosum in the resected iliac arterial tissue. The tissue histopathology revealed evidence of chronic vasculitis with granulation tissue and thrombus on the anterior tibialis and the posterior tibialis up to the proximal margin of femoral arteries, but the special stains failed to demonstrate any etiologic agent, including Pythium spp. After the surgery, the patient was given P. insidiosum immunotherapeutic vaccine (provided by Ariya Chindamporn, Chulalongkorn University, Bangkok; CUH Lot 140207/15-302), as well as the antifungal drugs, terbinafine at a dosage of 125 mg twice daily (13 mg/kg/day) and itraconazole at a dosage of 80 mg twice daily (8 mg/kg/day) for 2 months. The patient remained well and was discharged after almost 2 months after admission. Follow-up CTA performed 10 weeks after the amputation did not reveal recurrence of the disease. At the time of this communication, the patient has been symptom-free for 2 years.