The scientific background in expert-opinion papers for recommending Computed Tomography (CT) in unilateral pleural exudates is based on studies including patients with other findings than unilateral pleural effusions or selected patients undergoing thoracoscopy. Therefore, we performed a systematic review investigating the sensitivity of CT for predicting malignancy in patients with unilateral, non-transudative, pleural effusions. A search strategy was developed with the assistance of a medical information specialist at our university library. We searched PubMed/MEDLINE, EMBASE and Cochrane Library, ClinicalTrials.gov and articles citing the included studies. No date restrictions were applied (the first included paper was published in 2001 (1)), and only literature in English was included. We used the Quality Assessment of Diagnostic Accuracy Studies 2 for bias assessment. We registered the protocol at PROSPERO (CRD42018094830). Five studies were included, two prospective and three retrospective, all performed in Western Europe. No study reported diagnostic values for patients with unilateral, non-transudative pleural effusions only; one study did for unilateral pleural effusions. In the remaining studies, most patients had unilateral effusions and non-transudative effusions. Patients were primarily males and >70 years. All but one study found a high incidence of malignancy, dominated by malignant pleural mesothelioma. All studies were limited by risk of bias and applicability, predominantly regarding study population, pretests and index test. The current evidence supporting the sensitivity of CT for predicting malignancy in unilateral pleural effusions (both non-transudative and all types of effusion) is very low and did not allow meta-analysis. Standardization of patient population and CT protocol may facilitate conclusions of futures studies.