Detecting delirium in elderly emergency patients is critical to their outcome. The Nursing Delirium Screening Scale (Nu-DESC) is a short, feasible instrument that allows nurses to systematically screen for delirium. This is the first study to validate the Nu-DESC in a German emergency department (ED). The Nu-DESC was implemented in a high-volume, interdisciplinary German ED. A consecutively recruited sample of medical patients aged ≥ 70 years was screened by assigned nurses who performed the Nu-DESC as part of their daily work routine. The results were compared to a criterion standard diagnosis of delirium. According to the criterion standard diagnosis, delirium was present in 47 (14.9%) out of the 315 patients enrolled. The Nu-DESC shows a good specificity level of 91.0% (95% CI 87.0-94.2), but a moderate sensitivity level of 66.0% (95% CI 50.7-79.1). Positive and negative likelihood ratios are 7.37 (95% CI 4.77-11.36) and 0.37 (95% CI 0.25-0.56), respectively. In an exploratory analysis, we find that operationalizing the Nu-DESC item "disorientation" by specifically asking patients to state the day of the week and the name of the hospital unit would raise Nu-DESC sensitivity to 77.8%, with a specificity of 84.6% (positive and negative likelihood ratio of 5.05 and 0.26, respectively). The Nu-DESC shows good specificity but moderate sensitivity when performed by nurses during their daily work in a German ED. We have developed a modified Nu-DESC version, resulting in markedly enhanced sensitivity while maintaining a satisfactory level of specificity.