To evaluate the potential bias of analyzing aggregated data, we separately examined antibiotic exposure and resistance data for 35,423 patients admitted to a university hospital in Utah, from both an individual-patient perspective and group-level perspective. From 1994 through 1998, use of defined daily doses (per 1000 patient-days) of fluoroquinolones, third-generation cephalosporins, ampicillin-sulbactam, and imipenem increased by 82%, 38%, and 99%, and decreased by 38%, respectively, whereas group-level resistance rates of Enterobacteriaceae or Pseudomonas species changed only minimally. However, in individual-patient-level analyses performed by multivariable proportional hazards regression, exposure to a fluoroquinolone, third-generation cephalosporin, ampicillin-sulbactam, or imipenem was a strong risk factor for resistance to fluoroquinolones (adjusted hazard ratio [AHR], 4.0; P<.001), third-generation cephalosporins (AHR, 3.5; P<.001), ampicillin-sulbactam (AHR, 2.3; P = .008), or imipenem (AHR, 5.7; P<.001), respectively. Thus, group-level and individual-patient-level analyses of antibiotic-use-versus-susceptibility relations yielded divergent results. Multicenter studies should include individual-patient-level data to elucidate more fully the relation between antibiotic exposure and resistance.