Early identification of patients with a poorer prognosis in the Emergency Department (ED) is crucial for prompt treatment and resource allocation. We investigated the relationship between the Neutrophil to Lymphocyte Ratio (NLR) and 30-day mortality in elderly acute medical patients. Prospective single-center cohort study including consecutive patients admitted to the ED. Inclusion criteria were age > 65years and medical condition as the cause of ED access. Exclusion criteria were patients admitted for traumatic injuries or non-traumatic surgical diseases. ROC analysis was used to set the best cut-off of the NLR for mortality. 953 patients were included and 142 (14.9%) died during follow-up. ROC analysis showed a good predictive value of the NLR with an AUC 0.70, 95%CI 0.67-0.73 (p < 0.001) and identified a NLR > 8 as the best cut-off. Patients with NLR > 8 had a more serious triage code (72.6% had a triage code ≤ 2) and an increased heart rate and body temperature. They more often presented with dyspnea, abdominal pain, falls and vomiting. They also were characterized by an increase in urea, creatinine, white blood cells, neutrophils, fibrinogen, D-dimer, glycemia, CRP, LDH and transaminases and by a decrease in eGFR, of lymphocytes and monocytes. Multivariable logistic regression analysis demonstrated that the NLR remained associated with mortality after adjustment for confounders (Odds ratio 2.563, 95%CI 1.595-4.118, p < 0.001). Patients with NLR > 8 showed a higher mortality rate. NLR is an easy and inexpensive tool that may be used for risk stratification in the ED. The results of this study need to be validated in larger external cohorts.