Introduction: Pericardiocentesis is a procedure performed for diagnostic and therapeutic purposes, and it consists in draining the pericardial effusion liquid in sterile conditions. The accumulation of fluid in the pericardial space may be caused by several systemic conditions, including viral or bacterial infections, autoimmune disease, cancer, as well as thyroid mal- function. A rapidly growing pericardial effusion can lead to cardiac tamponade, and conse- quently to acute hypodiastolic heart failure. Case report: We report the case of a 79-year-old female, without previously known cardiovascular pathologies, who presented to the Emer- gency Room due to a gradual deterioration in her health status. Imaging procedures included a chest X-ray and an echocardiography that confirmed the diagnosis of pericardial effusion. Pericardiocentesis was performed using cardiac ultrasound guidance, resulting in the drain- ing of a small quantity of yellowish, partly haemorrhagic fluid. The patient’s general condi- tion did not improve, thus another pericardiocentesis was carried out, this time with fluo- roscopical and cardiac ultrasound guidance, and 1200 milliliters of sero-haemorrhagic fluid was drained. The laboratory analysis revealed that the patient had hypothyroidism, and the cytological analysis of the drained pericardial fluid excluded a neoplastic origin, tuberculosis, and other infectious etiologies. The particularity of the case consists in a pericardial effusion evolving into cardiac tamponade, for which the pericardiocentesis was guided using echocar- diographic, fluoroscopic and radiologic methods, because simple ultrasound-guided drainage was not efficient. Conclusion: The superiority of a combined imaging-guided approach in cases of pericardial effusion recommends it as an alternative to a surgical procedure, guided solely by echocardiography, which is often used in cases of unsuccessful drainage of pericar- dial effusion fluid.