Objectives: The aim of this study was to determine the markers that can reduce unnecessary invasive procedures by revealing the presence of benign pleural effusion (BPE) in patients with exudative pleural effusion.

Methods: A total of 624 patients from three prospective studies were included in the study. Patients diagnosed with BPE were followed up for at least 18 months to confirm the benign nature of the disease. Patients' clinical, laboratory, and radiological data were analyzed for findings suggestive of BPE using multiple hierarchical logistic regression analysis.

Results: Of the 624 patients in the study, 220 (35.3%) were diagnosed with BPE and 404 (64.7%) with MPE. TB was diagnosed in 72 (32.7%) of the patients with BPE. MPM was diagnosed in 201 (49.8%) of patients with MPE. The mean age of patients with BPE was 56.9 years, and that of patients with MPE was 64.3 years (p<0.001). In multivariate analysis, younger age (p=0.021), male patients (p=0.004), absence of cell ball in the fluid (p=0.022), higher sedimentation values (p=0.001), fluid glucose (p=0.044) and protein levels (p=0.021), absence of massive fluid on chest X-ray (p<0.001), absence of pleural thickening, nodular pleural involvement, mass (p=0.002), frozen chest (p<0.001) and mediastinal pleural involvement (p=0.012) at CT were found to be predictors of the presence of BPE. Those scoring greater than 0.50 in the regression model accounted for 3/4 of patients with BPE.

Conclusion: The results of this study demonstrate that the workload, cost, and complication burden of unnecessary invasive procedures can be reduced by creating marker combinations to distinguish patients with BPE.