Background. An initial step in the evaluation of patients with pleural effusion syndrome (PES) is to determine whether the pleural fluid is a transudate or an exudate. Objectives. To investigate total adenosine deaminase (ADA) as a biomarker to classify pleural transudates and exudates. Methods. An assay of total ADA in pleural fluids (P-ADA) was observed using a commercial kit in a population-based cohort study. Results. 157 pleural fluid samples were collected from untreated individuals with PES due to several causes. The cause most prevalent in transudate samples (21%,
n
=
33
/
157
) was congestive heart failure (79%, 26/33) and that among exudate samples (71%,
n
=
124
/
157
) was tuberculosis (28.0%, 44/124). There was no significant difference in the proportion of either sex between the transudate and exudate groups. The median values of P-ADA were significantly different (
P
<
0.0001
) between both total exudates (18.4 U/L; IQR, 9.85-41.4) and exudates without pleural tuberculosis (11.0 U/L; IQR, 7.25-19.75) and transudates (6.85; IQR, 2.67-11.26). For exudates, the AUC was 0.820 (95% CI, 0.751-0.877;
P
<
0.001
), with excellent discrimination. The optimum cut-off point in the ROC curve was determined as the level that provided the maximum positive likelihood ratio (PLR; 14.64; 95% CI, 2.11-101.9) and was22.0 U/L. For transudates, the AUC was 0.8245 (95% CI, 0.7470-0.9020;
P
<
0.0001
). Internal validation of the AUC after 1000 resamples was evaluated with a tolerance minor than 2%. The clinical utility was equal to 92% (95% CI, 0.84 to 0.96,
P
<
0.05
).Conclusions. P-ADA is a useful biomarker for distinguishing pleural exudates from transudates.