Introduction: According to clinical guidelines, there are no differences in early infection rates when utilizing antimicrobial prophylaxis regimens beyond 24 hours. We shortened the prophylaxis regimen from 72 to 24 hours in liver transplant recipients due to rising rates of resistance. The objective of this study is to evaluate the difference in posttransplant outcomes, following the protocol change. Design: We reviewed adult patients undergoing orthotopic liver transplantation between June 2013 and December 2015. Patients were stratified into 2 cohorts: 24 and 72 hours. Patients were excluded if donor cultures were positive. The primary objective of this study is to evaluate the incidence and time to posttransplant infections. The secondary objectives included analysis of total and intensive care unit length of stay and rates ofClostridioides difficileinfection. Results: Forty-four patients were included, 20 in the 72-hour and 24 in the 24-hour cohorts. The incidence of post-OLT infection (30% vs 8%,P= .115, 95% CI: -1% to 45%) was higher in the 72-hour cohort. Total (21 vs 14,P= .332, 95% CI: -4% to 28%) and intensive care unit LOS (11 vs 6,P= .201, 95% CI, -5% to 31%) were longer in the 72-hour group. No difference was observed in the incidence of CDI (15% vs 13%,P= 1.000). Discussion: There was no increase in posttransplant infections in the 24-hour cohort. Shorter antibiotic exposure may be associated with a reduction in length of stay and be favorable in this patient population.