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Backgrounds:The causes and prognosis of pericardial effusion (PE) may be different according to time, region, economy, and hospital. This study was performed to evaluate the etiology, clinical outcome, and prognosis of patients with large, symptomatic PE treated by echo-guided pericardiocentesis at Kangnam St. Mary's Hopital (the Catholic University of Korea, Seoul, Korea). Hypothesis: According to etiologies of large, symptomatic PE, the prognosis of patients may be different. Methods: We reviewed 116 consecutive patients who underwent echo-guided pericardiocentesis due to large, symptomatic PE over the last 12 y. The Kaplan-Meier survival curve with log-rank method was applied for the survival analysis.Results: Procedural success rate of echo-guided pericardiocentesis was 99.1%. Common causes of PE requiring pericardiocentesis were lung cancer (27.6%), tuberculosis (TB) (13.8%), and uremia (6.9%). The mortality rate of 6 mo after the pericardiocentesis was 80.3% in malignant PE, whereas the over-all mortality rate was 18.2% in nonmalignant PE (p<0.0001). Among the malignant PE, lung cancer (27.6%) and breast cancers (6.9%) were the most common causes. The mean cytologic detection rate and mean life expectancy of malignant PE were 44% and 5-7 mo. Patients with breast cancer and lymphoma had relatively better life expectancy (11.4 and 7.7 mo), whereas those with stomach cancer and metastases of unknown origin (MUO) had poorer prognosis (1.2 and 2.3 mo). The most common causes of nonmalignant PE were TB, uremia, and iatrogenic, and their mean life expectancy was approximately 54 mo. Conclusions: Malignancy, especially lung cancer and TB, were the most common causes of large symptomatic PE. The prognosis of large symptomatic PE was related to the underlying disease. Malignant PE was associated with the poorest prognosis.