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Background: Delirium has a high incidence pathology associated with negative outcomes. Although highly preventable, half the cases are not recognized. One major cause of delirium misdiagnosis is the absence of a versatile instrument to measure it. Aims: Our objective was to translate the nursing delirium screening scale (Nu-DESC) and evaluate its performance in Italian settings. Methods: This was a methodological study conducted in two sequential phases. The first was the Italian translation of Nu-DESC through a translation and back-translation process. The second aimed to test the inter-rater reliability, the sensibility and specificity of the instrument on a convenience sample of 101 hospitalized elderly people admitted to relevant wards of the San Gerardo Hospital in Monza. To evaluate the inter-rater reliability, two examiners tested Nu-DESC on 20 patients concurrently without comparison. To measure the sensibility and specificity of Nu-DESC, the confusion assessment method was used as a gold standard measure. Results: The inter-rater reliability (Cohen Kappa) was 0.87—an excellent agreement between examiners. The study of the ROC curve showed an AUC value of 0.9461 suggesting high test accuracy. Using 3 as a cut-off value, Nu-DESC showed 100 % sensibility and 76 % specificity. Discussion and conclusion: Further research is needed to test Nu-DESC on a larger sample. However, based on our results, Nu-DESC can be used in research and clinical practice in Italian settings because of its very good and similar performances to previous validation studies. The value of 3 appears to be the optimal cut-off in the Italian context.