A 49-year-old woman presented with severe abdominal pain and per rectal bleed, 13 days after receiving the first dose of the AstraZeneca vaccine. Blood tests showed remarkably low platelet count, unmeasurable D-dimer levels and low fibrinogen levels, consistent with a diagnosis of vaccine-induced thrombotic thrombocytopaenia and disseminated intravascular coagulation. CT mesenteric angiogram revealed massive portosplenic mesenteric vein thrombosis. CT head also noted non-occlusive thrombosis at several sites. She was treated with intravenous immunoglobulins, plasma exchange, anticoagulants and transjugular intrahepatic portosystemic shunt procedure. Following a prolonged inpatient stay, she was discharged with subsequent short bowel syndrome and long-term parenteral nutrition. This particular clinical scenario aims to highlight the importance for clinicians to remain vigilant for rare complications associated with the AstraZeneca vaccine and the subsequent management involved, at a time where it is vital to vaccinate globally in order to control the spread of the COVID-19 pandemic.