Fluoroquinolones and third-generation cephalosporins are particularly prone to select bacterial resistance to antibiotics. We aimed to assess the temporal trends of antibiotic use in the emergency department adults unit of an academic hospital between 2002 and 2012. Antibiotic use was converted in defined daily doses (DDD). The total antibiotic consumption tended to decrease, from 53.1±8.5 to 48.6±11.9 DDD/1000 patient visits (estimate decrease per year, -0.9±0.5 DDD/1000 visits, P=0.07). Use of third-generation cephalosporins increased significantly, from 9.7% of total antibiotic use to 22.6% (estimate per year, 1.2±0.2%, P<0.0001), whereas use of fluoroquinolones decreased from 19.5 to 12.3% (estimate per year, -0.7±0.2%, P<0.003). Given their ability to select bacterial resistance, especially extended-spectrum β-lactamases, particular attention should be paid to increasing use of third-generation cephalosporins in the emergency department.