Cardiac tamponade is defined as an accumulation of fluid within the pericardial sac that is large enough to impair the diastolic filling of the ventricles. There are numerous causes, including cardiac disease, malignancy, and trauma (penetrating, blunt, and iatrogenic). With increasing complexity of percutaneous endovascular interventions, interventional radiologists must learn to recognize the preexisting and iatrogenic presence of cardiac tamponade during procedures and be familiar with its treatment. Two cases of pericardial tamponade complicating central venous interventions are described. In addition, the clinical condition is discussed and its diagnosis and treatment are reviewed.