Objectives: Although transudative pleural effusions are generally associated with benign conditions, a subset may represent malignant pleural effusions (MPE). Because pleural fluid cytology is often not performed in transudative effusions, malignancy may be underdiagnosed. We aimed to identify predictors of malignancy in transudative pleural effusions and develop a clinical prediction score. Methods: We conducted a retrospective cohort study including patients with transudative pleural effusion who underwent pleural fluid cytological analysis between January 2022 and January 2026 at a tertiary chest diseases center. Among 3253 patients who underwent thoracentesis, 314 patients with transudative pleural effusions were included. Clinical, radiological, laboratory, and pleural fluid characteristics were analyzed. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of MPE. A simplified risk score was developed from the final multivariable model and internally validated using bootstrap resampling. Results: Among 314 patients, 24 (7.6%) were diagnosed with MPE. In multivariable analysis, pleural pathology on thoracic computed tomography (CT) (OR 7.07, 95% CI 2.61–19.16), parenchymal nodule/mass OR 5.18, 95% CI 1.85–15.54), pleural fluid lactate dehydrogenase (LDH) > 150 U/L (OR 5.09, 95% CI 1.86–13.93), and pleural fluid glucose < 100 mg/dL (OR 3.52, 95% CI 1.12–11.1) were independent predictors of MPE. The 16-point scoring system showed excellent discriminative performance (AUC 0.89). Bootstrap validation confirmed good calibration and model robustness. Conclusions: In patients with transudative pleural effusions, pleural pathology on thoracic CT, parenchymal nodule or mass, pleural fluid LDH > 150 U/L, and pleural fluid glucose < 100 mg/dL were independent predictors of MPE. A simple 16-point prediction score derived from these variables demonstrated excellent discriminative performance and may assist in identifying patients who warrant pleural fluid cytological evaluation despite transudative pleural fluid characteristics.