BACKGROUND: The direCt Lung Ultrasound Evaluation (CLUE) technique was proven to be an accurate method for monitoring extravascular lung water in donor lungs during ex vivo lung perfusion (EVLP) in an experimental model. The aim of this study was to examine the application of CLUE in the clinical setting. METHODS: Lungs were evaluated using acellular EVLP protocol. Ultrasound images were obtained directly from the lung surface. Images were graded according to the percentage of B-lines seen on ultrasound. CLUE scores were calculated at the beginning and end of EVLP for the whole lung, each side, and lobe based on the number (No.) of images in each grade and the total No. of images taken and evaluated retrospectively. RESULTS: A total of 23 EVLP cases were performed resulting in 13 lung transplants (LTxs) with no hospital mortality. Primary graft dysfunction (PGD) occurred in only 1 recipient (PGD3, no PGD2). Significant differences were found between suitable and non-suitable lungs in CLUE scores (1.03 vs 1.85, p < 0.001), unlike the partial pressure of oxygen/fraction of inspired oxygen ratio. CLUE had the highest area under the receiver operating characteristic curve (0.98) compared with other evaluation parameters. The initial CLUE score of standard donor lungs was significantly better than marginal lungs. The final CLUE score in proned lungs showed improvement when compared with initial CLUE score, especially in the upper lobes. CONCLUSIONS: The CLUE technique shows the highest accuracy in evaluating donor lungs for LTx suitability compared with other parameters used in EVLP. CLUE can optimize the outcomes of LTx by guiding the decision making through the whole process of clinical EVLP.