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Background Limited and conflicting data exist evaluating low-bioavailability oral antibiotics (LOW) for definitive treatment of Enterobacteriaceae bacteremia (EB), and existing dogma limits their use. We compared outcomes for EB from a suspected urine source with LOW vs. high-bioavailability oral antibiotics (HIGH). Methods This was a retrospective cohort study across Veterans Affairs hospitals from 2006 to 2015. Inclusion criteria were monomicrobial EB and matching urine culture; receipt of active, empiric parenteral antibiotic(s); and conversion to a single oral LOW or HIGH between treatment day 2 and 6. Exclusion criteria were EB in the previous year, prior urologic abscess, or chronic prostatitis. HIGH included fluoroquinolones or trimethoprim-sulfamethoxazole. LOW included oral β-lactams. The primary outcome was all-cause 30-day mortality or recurrent EB. Patients were weighted using propensity-based overlap weights to make the groups more similar to each other at baseline. Log binomial regression models were used to estimate relative risks and risk differences. Results A total of 4,090 patients met inclusion criteria with 955 LOW and 3,135 HIGH. The median days of parenteral antibiotics before conversion to oral antibiotics were 4 (IQR 3, 5) in LOW and 4 (IQR 3, 4) in HIGH. The composite primary outcome occurred in 42 (4.4%) LOW and 94 (3.0%) HIGH. The adjusted relative risk (aRR) of the composite primary outcome with LOW was 1.28 (95% CI 0.86–1.89; risk difference [RD] 0.9%). Recurrent EB within 30-days occurred in 14 (1.5%) LOW and 12 (0.4%) HIGH (aRR 3.24, 95% CI, 0.46–22.8; RD 1.0%). Thirty-day mortality occurred in 29 (3.0%) LOW and 82 (2.6%) HIGH (aRR 1.0, 95% CI, 0.66–1.52; RD 0%). Similar outcomes were observed at 90 days. Conclusion There was no difference in the composite outcome of 30-day mortality and recurrent bacteremia comparing hospitalized patients who received LOW vs. HIGH for the definitive treatment of EB from a suspected urine source. While there was a nonsignificantly higher risk of 30-day recurrent EB with LOW, the absolute risk and risk difference were small, suggesting that definitive therapy with LOW may be considered. Future evaluation is needed to better understand risk factors for recurrent EB and which patients may fail LOW. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]