Objective: To assess the value of pericardial fluid adenosine deaminase (ADA) and pericardial lysozyme (Lys) as tools in diagnosing tuberculous pericarditis. Methods: Forty-one patients (age range 17–77 years) with significant pericardial effusion were included in the study. Diagnostic pericardiocentesis and pericardial biopsy were performed while serum and pericardial fluid ADA and Lys were measured in all patients. Grouping of patients resulted as follows: group I = 7 patients with tuberculous pericarditis; group II = patients with neoplastic pericarditis; group III = 30 patients with idiopathic pericarditis. Results: Pairwise multiple comparison procedures revealed a significant difference of ADA in group I versus group III (p < 0.05) but not versus group II. Furthermore, pericardial Lys in group I was higher than in groups II and III (p < 0.05). A strong correlation between pericardial ADA and Lys was found (r = 0.733, p = 0.01) for all the patients. Receiver operating curves showed a value of 72 U/l as cutoff point of pericardium ADA, with a sensitivity of 100% and a specificity of 94% in the diagnosis of tuberculous pericarditis. Similarly for pericardial Lys, a value of 6.5 µg/dl had a sensitivity and specificity of 100 and 91.17%, respectively. Conclusions: Both measurements of pericardial ADA and Lys need to be taken into account when attempting the early diagnosis of tuberculous pericarditis.