Pericardial Decompression Syndrome (PDS) is an uncommon but life-threatening complication following pericardiocentesis for cardiac tamponade. We report PDS after pericardiocentesis in two patients that presented to the emergency department with cardiac tamponade. In both cases, pericardiocentesis was performed under ultrasound guidance using the left parasternal approach and approximately 1200–1500 mL of pericardial fluid was removed. Immediately after pericardiocentesis, the haemodynamic status of the patients improved. However, 2–3 h post decompression, both patients developed hypotension and pulmonary edema with reduced left ventricular function, suggestive of PDS. PDS is a condition that is described as paradoxical worsening of vital signs after successful decompression of the pericardium in the setting of acute tamponade. Three possible mechanisms explaining PDS are ischaemic, hemodynamic and autonomic processes. If PDS is unrecognized and untreated, it is associated with a high mortality rate secondary to pulmonary edema and cardiogenic shock. If managed urgently, the cardiopulmonary dysfunction in PDS is usually transient and largely reversible with supportive care.