Thoracentesis is one of the most commonly performed medical procedures with an excellent safety profile. We describe 2 patients, both of whom developed 2 very rare complications after image-guided thoracentesis. Both patients developed clinically relevant reexpansion pulmonary edema (RPE). Within 2 weeks of their first thoracentesis, both patients underwent a second thoracentesis, which was complicated by a large pneumothorax requiring drainage by tube thoracostomy. Pneumothorax and RPE are independent rare complications (<1%) that occur after thoracentesis. The development of these unusual complications in the same sequence in these 2 patients suggests that there may be a causal relationship between pneumothorax and RPE after sequential thoracenteses. Further investigations are necessary to better describe the underlying pathophysiology and mechanism that may explain this association.