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Background: The biochemical analysis of pericardial fluid for differentiating transudate from exudate is often ordered and interpreted according to the criteria extrapolated from pleural effusions. However, the validity of this discrimination when applied to pericardial effusion is under question., Methods: Patients who underwent pericardiocentesis between January 2004 and February 2014 were identified. Among them, 216 had essential medical records available and constituted the study population. The parameters specifically analyzed were the following: lactate dehydrogenase, total protein and glucose concentrations in both pericardial fluid and serum; pericardial fluid/serum ratios of lactate dehydrogenase and total protein content; and pH and specific gravity of pericardial fluid., Results: Eighty-one percent of pericardial effusions were classified as exudate according to Light's criteria. Both exudate and transudate fluid characteristics were possible for all etiological causes except for tuberculosis in which all were exudates. Although multiple cutoff points for all parameters were tested, significant overlap between different causes persisted (all having an area under the receiver operating characteristic curve of < 0.7). Thus, a reasonable accuracy to differentiate one cause from another could not be achieved., Conclusions: Although often ordered, the biochemical analysis of pericardial fluid has almost no diagnostic value to distinguish among causes of pericardial effusion in contemporary medicine.