© 2015 Wolters Kluwer Health, Inc. All rights reserved. Enteric fever in high-income countries is diagnosed mainly in patients returning from endemic countries. We assess the clinical, microbiological, and prognosis aspects of enteric fever in 2 Spanish tertiary hospitals. A retrospective observational study was conducted at Vall d'Hebron University Hospital and Ramón y Cajal University Hospital in Spain. We reviewed medical records of all patients who were diagnosed with enteric fever from January 2000 to January 2014 at these hospitals. We identified 47 patients with enteric fever episodes. According to their travel history, 35 (74.5%) patients had travelled to highly endemic countries. Imported enteric fever was acquired mainly in Asia (70.3%). Imported infections were implicated in travelers (48.6%), visiting friends and relatives (40%) and immigrants (11.4%). We found that 12 patients were diagnosed with enteric fever without a travel history (autochthonous infection). The resistance profile of the isolates showed decreased ciprofloxacin susceptibility in 66.7% of the imported group and 8.3% of the autochthonous group (P=0.001). Salmonella strains from patients returning from Asia had an increased risk of having decreased ciprofloxacin susceptibility (odds ratio, 52.25; 95% confidence interval: 8.6-317.7). Patients with imported enteric fever are at higher risk for having a Salmonella strain with decreased ciprofloxacin susceptibility, especially in patients returning from Asia. Initial treatment with third-generation cephalosporin or azithromycin is strongly recommended until a drug-susceptibility test is available. Prevention strategies such as pretravel counseling and immunization before travel may be beneficial.