BACKGROUND:Electronic health records provide the opportunity to assess system-wide quality measures. Veterans Affairs Pharmacy Benefits Management Center for Medication Safety uses medication use evaluation (MUE) through manual review of the electronic health records. OBJECTIVE:To compare an electronic MUE approach versus human/manual review for extraction of antibiotic use (choice and duration) and severity metrics. RESEARCH DESIGN:Retrospective. SUBJECTS:Hospitalizations for uncomplicated pneumonia occurring during 2013 at 30 Veterans Affairs facilities. MEASURES:We compared summary statistics, individual hospitalization-level agreement, facility-level consistency, and patterns of variation between electronic and manual MUE for initial severity, antibiotic choice, daily clinical stability, and antibiotic duration. RESULTS:Among 2004 hospitalizations, electronic and manual abstraction methods showed high individual hospitalization-level agreement for initial severity measures (agreement=86%-98%, κ=0.5-0.82), antibiotic choice (agreement=89%-100%, κ=0.70-0.94), and facility-level consistency for empiric antibiotic choice (anti-MRSA r=0.97, P<0.001; antipseudomonal r=0.95, P<0.001) and therapy duration (r=0.77, P<0.001) but lower facility-level consistency for days to clinical stability (r=0.52, P=0.006) or excessive duration of therapy (r=0.55, P=0.005). Both methods identified widespread facility-level variation in antibiotic choice, but we found additional variation in manual estimation of excessive antibiotic duration and initial illness severity. CONCLUSIONS:Electronic and manual MUE agreed well for illness severity, antibiotic choice, and duration of therapy in pneumonia at both the individual and facility levels. Manual MUE showed additional reviewer-level variation in estimation of initial illness severity and excessive antibiotic use. Electronic MUE allows for reliable, scalable tracking of national patterns of antimicrobial use, enabling the examination of system-wide interventions to improve quality.