OBJECTIVE: Patients that initially appear stable on arrival to the hospital often have less intensive monitoring of their vital signs, possibly leading to excess mortality. The aim was to describe risk factors for deterioration in vital signs and the related prognosis among patients with normal vital signs at arrival to a medical emergency department (MED). DESIGN AND SETTING: Single-centre, retrospective cohort study of all patients admitted to the MED from September 2010-August 2011. SUBJECTS: Patients were included when their vital signs (systolic blood pressure, pulse rate, respiratory rate, Glasgow Coma Scale, oxygen saturation and temperature) were within the normal range at arrival. Deterioration was defined as a deviation from the defined normal range 2-24 hours after arrival. RESULTS: 4292 of the 6257 (68.6%) admitted to the MED had a full set of vital signs at first presentation, 1440/4292 (33.6%) had all normal vital signs and were included in study, 44.0% were male, median age 64 years (5th/95th percentile: 21-90 years) and 446/1440 (31.0%) deteriorated within 24 hours. Independent risk factors for deterioration included age 65-84 years odds ratio (OR): 1.79 (95% confidence interval [CI]: 1.27-2.52), 85+ years OR 1.67 (95% CI: 1.10-2.55), Do-not-attempt-to-resuscitate order OR 3.76 (95% CI: 1.37-10.31) and admission from the open general ED OR 1.35 (95% CI: 1.07-1.71). Thirty-day mortality was 7.9% (95% CI: 5.5-10.7%) among deteriorating patients and 1.9% (95% CI: 1.2-3.0%) among the non-deteriorating, hazard ratio 4.11 (95% CI: 2.38-7.10). CONCLUSIONS: Among acutely admitted medical patients who arrive with normal vital signs, 31.0% showed signs of deterioration within 24 hours. Risk factors included old age, Do-not-attempt-to-resuscitate order, admission from the open general ED. Thirty-day mortality among patients with deterioration was four times higher than among non-deteriorating patients. Further research is needed to determine whether intensified monitoring of vital signs can help to prevent deterioration or mortality among medical emergency patients.