Purpose: To evaluate the value of CEUS in differentiating malignant from benign pleural effusions (PEs). Methods: From 2008 to 2017, 83 patients with PEs of unknown cause were examined using B-mode thoracic ultrasound (B-TUS), CEUS, and cytological examination. The extent of enhancement of the pleural thickening, the presence of enhancement of septa or a solid mass within the PE, and the homogeneity of the enhancement in the associated lung consolidation, were examined. Subsequently, the diagnostic value of cytology, B-TUS, and CEUS in differentiating malignant from benign PEs was determined. Results: With CEUS, markedly enhanced pleural thickening and inhomogeneous enhanced lung consolidation were significantly more frequently associated with malignancy (p < 0.05). In the subgroup analysis, the use of CEUS increased the sensitivity from 69.2 to 92.3 in patients with initial negative cytology but clinical suspicion of malignant PE; it also increased the specificity from 63.0 to 90.0, the positive predictive value from 69.2 to 92.3, the negative predictive value from 63.0 to 90.0, and the diagnostic accuracy from 66.7 to 87.5, in the evaluation of PE malignancy. Conclusion: The use of clinically based B-TUS and CEUS as a complementary method to cytological evaluation may be beneficial for evaluating a PE of unknown cause. CEUS patterns of enhanced pleural thickening and inhomogeneous enhanced lung consolidation may suggest a malignant PE.