We compared the direct E-test susceptibility testing (DET) on respiratory samples with a standard microbroth dilution method (MBD) after quantitative cultures. A total of 152 samples from intensive care unit patients were processed by DET onto Mueller-Hinton agar. Oxacillin, piperacillin/tazobactam, cefepime, imipenem, ciprofloxacin, and amikacin were the antimicrobials evaluated. Cultures were 102 monomicrobials and 50 polymicrobials. Overall, 93.8% of the isolates were recovered by the DET. Among the 772 microorganism-antibiotic combinations evaluated, there was a total agreement with the MBD in 96.1%. There were 8 very major errors (1.03%), 15 major (1.94%), and 7 minor (0.91%). All discrepancies but one corresponded to polymicrobial cultures, and most occurred with cefepime (8 cases, 7.07%) and imipenem (7 cases, 6.18%). Readings of DET were easy to interpret and improved with transmitted light. DET on respiratory samples is a rapid technique that provides susceptibility results in 18 to 24 h comparable with these obtained by MBD.