Acute portal vein thrombosis (PVT) is a complication of liver cirrhosis. The presence of viral infections such as hepatitis B (HBV) and hepatitis C (HCV) can further increase cirrhotic patients’ risk of developing PVT, especially in the rare case when there is superinfection with both HBV and HCV.We present a patient with HCV cirrhosis whose clinical condition was decompensated secondary to the development of superimposed HBV infection, who developed acute PVT during hospitalization. This case offers a unique presentation of acute PVT that developed within several days of hospitalization for decompensated liver disease, as proven by the interval absence of portal venous flow on repeat imaging. Despite the workup on the initial presentation being negative for PVT, reconsideration of differentials after the change in our patient’s clinical status led to the diagnosis. Active HBV infection was likely the initial trigger for the patient’s cirrhosis decompensation and presentation; the subsequent coagulopathy and alteration in the portal blood flow triggered the development of an acute PVT.The risk for both prothrombotic and antithrombotic complications remains high in patients with cirrhosis, a risk that is vastly increased by the presence of superimposedinfections. The diagnosis of thrombotic complications such as PVT can be challenging, thus stressing the importance of repeat imaging in instances where clinical suspicion remains high despite negative imaging. Anticoagulation should be considered for cirrhotic patients with PVT on an individual basis for both prevention and treatment. Prompt diagnosis, early intervention, and close monitoring of patients with PVT are crucial for improving clinical outcomes. The goal of this report is to illustrate diagnostic challenges that accompany the diagnosis of acute PVT in cirrhosis, as well as discuss therapeutic options for optimal management of this condition.