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To assess the diagnostic value and determinants of nurses’ clinical impression for the recognition of children with a serious illness on presentation to the emergency department (ED).Secondary analysis of a prospective cohort.6390 consecutive children <16 years of age presenting to a paediatric ED with a non-surgical chief complaint and complete data available.Diagnostic accuracy of nurses’ clinical impression for the prediction of serious illness, defined by intensive care unit (ICU) and hospital admission. Determinants of nurses’ impression that a child appeared ill.Nurses considered a total of 1279 (20.0%) children appearing ill. Sensitivity of nurses’ clinical impression for the recognition of patients requiring ICU admission was 0.70 (95% CI 0.62 to 0.76) and specificity was 0.81 (95% CI 0.80 to 0.82). Sensitivity for hospital admission was 0.48 (95% CI 0.45 to 0.51) and specificity was 0.88 (95% CI 0.87 to 0.88). When adjusted for age, gender, triage urgency and abnormal vital signs, nurses’ impression remained significantly associated with ICU (OR 4.54; 95% CI 3.09 to 6.66) and hospital admission (OR 4.00; 95% CI 3.40 to 4.69). Ill appearance was positively associated with triage urgency, fever and abnormal vital signs and negatively with self-referral and presentation outside of office hours.The overall clinical impression of experienced nurses at the ED is on its own, not an accurate predictor of serious illness in children, but provides additional information above some well-established and objective predictors of illness severity.