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Children travelling are potentially exposed to a wide spectrum of illness, which includes not only mild self-limiting disease but also severe illness requiring hospitalization. Risk factors for hospitalization need to be analyzed to inform prevention and treatment strategies for travel-related disease, to make travelling for children—from a medical perspective—more secure.We performed a cross-sectional analysis on children with travel-related disease presenting at the Emergency Room of University of Zurich Children’s Hospital between July 2007 and December 2012. The profile of children being hospitalized was compared with that of children treated as outpatients.Eight hundred and one children (57.4% male) were included in the study. Eighty-three children (10.4%) were treated as inpatients. Compared with outpatients, inpatients were significantly more likely to be male, to have travelled to Southern Asia, to have a diagnosis of Salmonella typhi or Salmonella paratyphi (3.6 % vs. 0.1%, P < 0.0001), pyogenic abscess (3.6% vs. 0.1 %, P < 0.0001) or malaria (1.4 % vs. 0.2%, P = 0.0384). Neurologic diagnoses (such as seizure disorder: 3.6% vs. 0.4%, P < 0.0001) were diagnosed more often among inpatients. Furthermore, inpatients presented more often with nonspecific findings such as dehydration (8.5% vs. 0.6%, P < 0.0001). No correlation with inpatient care was seen for visiting friends and relatives/immigrant travel.Children acquire a wide spectrum of travel-related illness. A careful, detailed travel history is important in children presenting in the emergency room with symptoms suggesting infectious disease.