Abstract Background In this pilot trial, we evaluated whether audit-and-feedback was a feasible strategy to improve antimicrobial prescribing in emergency departments (EDs). Methods We evaluated an audit-and-feedback intervention using a quasi-experimental interrupted time-series design at 2 intervention and 2 matched-control EDs; there was a 12-month baseline, 1-month implementation, and 11-month intervention period. At intervention sites, clinicians received (1) a single, one-on-one education about antimicrobial prescribing for common infections and (2) individualized feedback on total and condition-specific (uncomplicated acute respiratory infection [ARI]) antimicrobial use with peer-to-peer comparisons at baseline and every quarter. The primary outcome was the total antimicrobial-prescribing rate for all visits and was assessed using generalized linear models. In an exploratory analysis, we measured antimicrobial use for uncomplicated ARI visits and manually reviewed charts to assess guideline-concordant management for 6 common infections. Results In the baseline and intervention periods, intervention sites had 28 016 and 23 164 visits compared to 33 077 and 28 835 at control sites. We enrolled 27 of 31 (87.1%) eligible clinicians; they acknowledged receipt of 33.3% of feedback e-mails. Intervention sites compared with control sites had no absolute reduction in their total antimicrobial rate (incidence rate ratio = 0.99; 95% confidence interval, 0.98–1.01). At intervention sites, antimicrobial use for uncomplicated ARIs decreased (68.6% to 42.4%; P < .01) and guideline-concordant management improved (52.1% to 72.5%; P < .01); these improvements were not seen at control sites. Conclusions At intervention sites, total antimicrobial use did not decrease, but an exploratory analysis showed reduced antimicrobial prescribing for viral ARIs. Future studies should identify additional targets for condition-specific feedback while exploring ways to make electronic feedback more acceptable.