Endobronchial ultrasound with transbronchial needle aspiration (TBNA) is commonly performed for the evaluation of mediastinal lymphadenopathy. Purulent pericarditis is a rare, yet potentially fatal complication of TBNA. It commonly presents with nonspecific symptoms such as chest pain, shortness of breath, palpitations, or vague abdominal discomfort. Additionally, more severe symptoms such as cardiac tamponade and even death have been reported. In this article, we present the case of a 58-year-old male who developed purulent pericardial effusion with tamponade thought to be caused by TBNA cytology. This case raises an important question regarding the current guidelines for prophylactic antibiotic treatment for patients at high risk of developing purulent pericarditis as a complication of TBNA.