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We describe the case of a 64 years-old woman admitted to the Emergency Department of the ASST-Spedali Civili of Brescia with fever and gastrointestinal symptoms 10 days after the first dose of ChAdOx1 nCov-19 vaccine. Laboratory investigations showed severe thrombocytopenia and high D-dimer, while an abdominal CT scan reported a partially occluding thrombosis of the superior mesenteric artery. Following treatment with fondaparinux, immunoglobulins and high dosage steroid therapy, we observed a rapid improvement of patient’s conditions. An ELISA assay showed the presence of antibodies against heparin PF4-complex. Subsequent abdominal CT-scan showed the superior mesenteric artery thrombosis resolution, and the patient was finally discharged after 12 days of hospitalization. Several reports pointed to the venous system as the main district affected by Vaccine-Induced Thrombotic Thrombocytopenia (VITT), while a peculiar feature of this report is the involvement of the mesenteric arterial system. Further investigation of VITT’s pathophysiological mechanisms is mandatory to develop preventive strategies and effective treatments.