*Purpose: The purpose of this study was to evaluate safety and efficacy endpoints of a revised post-operative antibiotic prophylaxis protocol in orthotopic liver transplant (OLT) patients, which was revised to conform to institutional stewardship efforts to limit antibiotic use.

*Methods: This is a retrospective single-center cohort study. Prior to the protocol change (routine group), OLT patients routinely received antibiotics for 3 days post-operatively. The revised protocol (limited group) called for no post-operative antibiotics unless the patient was considered to be high risk (secondary peritonitis) for infection. Patients were included if they were 18 years of age and older and underwent OLT at this center from January 2016 to September 2019. Patients were excluded if they received antibiotics for positive donor cultures or other post-OLT indications for antibiotics.

*Results: Two hundred and sixteen adult patients received OLT (118 and 98 in routine and limited groups respectively). There were no significant differences in the mean age (53.7 vs 55.5, p=0.221), sex, body mass index (29.6 vs 29.9, p=0.733), MELD (19.9 vs 18.7, p=0.268), roux-en-y hepaticojejunostomy (8% vs 7%, p=0.145), return to operating room (15% vs 14%, p=0.842), or living donor OLT (11% vs 7%, p=0.328) between the routine and limited groups. There was a significant difference in median days of therapy (DOT) between the routine and limited groups (2 vs 0, p<0.005). Significantly more patients in the routine vs limited groups received post-op antibiotics (64% vs 26%, p<0.005). In patients receiving antibiotics, there was no significant difference in median DOT between groups (4 vs 4, p=0.19). No significant difference was observed in rates of surgical site infection (SSI) (5.1% vs 12.2%, p=0.168) or Clostridioides difficile infection (6.7% vs 4.1%, p=0.381) between routine and limited groups respectively. No significant differences were observed in secondary outcomes of length of stay, death censored-graft survival, mortality at 30 days or infection during hospitalization.

*Conclusions: This study suggests that limiting post-OLT antibiotics in uncomplicated patients is safe based on non-significant differences in safety outcomes, including SSI.

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