The coxsackievirus is well known for its vastly differing clinical presentations.Patients with coxsackievirus usually present with a viral prodrome which can then progress to the cardiac symptoms of chest pain and/or palpitations.Most patients improve quickly with simply supportive care and nonsteroidal anti-inflammatory medications.However, coxsackievirus can also have more severe cardiac manifestations including myopericarditis, which can lead to cardiomyopathy and symptomatic heart failure.Specifically, coxsackievirus B is known as the “cardiotropic” strain that is involved in a large number of acute cardiac infections.The exact mechanism of cardiac myocyte injury is still not completely understood and these processes can lead to devastating consequences.An interesting presentation of a coxsackievirus B infection is cardiac tamponade.The majority of tamponade cases are seen with malignancy, trauma or autoimmune diseases.As such, coxsackievirus B is not typically considered amongst the differentials of cardiac tamponade.In this case, a 58-year-old male developed a large pericardial effusion leading to tamponade physiology.With other etiologies ruled out, it was determined that eoxsackievirus B was the culprit of this effusion.This unique presentation of coxsackievirus B reminds the medical practitioner of the potentially deadly course of this usually benign infection.This case also brings to attention the need for further research to identify individuals at risk for developing cardiac complications of coxsackievirus B infections.