The influence of hospital use of antibiotics other than cephalosporins and fluoroquinolones on extended-spectrum beta-lactamase (ESBL) resistance among Enterobacteriaceae is poorly known. Our objective was to explore the association between ESBL and hospital use of various classes of antibacterial agents. The relationship between monthly use of 19 classes of antibacterial agents and incidence of nosocomial ESBL-producing Enterobacteriaceae in a French hospital was studied between 2007 and 2013. Five antibiotic classes were significantly and independently associated with ESBL resistance. Uses of tetracyclines (link estimate ± SE, 0.0066 ± 0.0033), lincosamides (0.0093 ± 0.0029), and other antibacterial agents (0.0050 ± 0.0023) were associated with an increased incidence, while nitrofurantoin (-0.0188 ± 0.0062) and ticarcillin and piperacillin with or without enzyme inhibitor (-0.0078 ± 0.0031) were associated with a decreased incidence. In a multivariate model including 3rd- and 4th-generation cephalosporins, fluoroquinolones, amoxicillin, and amoxicillin-clavulanate, 3rd- and 4th-generation cephalosporins (0.0019 ± 0.0009) and fluoroquinolones (0.0020 ± 0.0008) were associated with an increased ESBL resistance, whereas amoxicillin and amoxicillin-clavulanate were not. Hospital use of tetracyclines and lincosamides may promote ESBL resistance in Enterobacteriaceae. Nitrofurantoin and ticarcillin and piperacillin with or without enzyme inhibitor should be considered as potential alternatives to broad-spectrum cephalosporins and fluoroquinolones to control the diffusion of ESBL resistance.