The defined daily dose, a popular measurement of antimicrobial use, may underestimate the use of antimicrobials that are dose-adjusted in patients with renal insufficiency. To evaluate the effect of renal dysfunction on these measures, we performed a retrospective cohort study that involved patients receiving ceftriaxone, levofloxacin, or vancomycin, with use of defined daily doses and 2 methods based on therapy duration--stop-start days (i.e., entire therapy duration) and transaction days (i.e., unique therapeutic days). The vancomycin use rate for patients with renal insufficiency was 36% lower than that of patients with normal renal function for defined daily doses, and it was 23% lower for transaction days; for levofloxacin, there was a 27% rate reduction for the defined daily dose. No significant reduction was noted when the stop-start day method was used. Compared with the defined daily dose method, measures of therapy duration are less affected by renal function and may improve comparisons between populations.