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Introduction: Early allograft dysfunction (EAD) is a life-threatening complication associated with liver transplantation, with a main risk factor being ischemia reperfusion injury (IRI). There is limited guidance available regarding pharmacologic prevention strategies for IRI, but there is a growing interest in using N-acetylcysteine (NAC). Recently, Methodist University Hospital (MUH) started utilizing NAC as pharmacologic prophylaxis for IRI in orthotopic liver transplant (OLT) patients. The purpose of this study was to compare rates of EAD in OLT recipients before and after the implementation of a NAC IRI protocol. Methods: This was a single-center, retrospective chart review at MUH from January 1st, 2023 to September 30th, 2023 and November 1st, 2023 to June 30th, 2024. Adult patients > 18 years old that received an OLT were eligible for inclusion. Patients were excluded if they expired within 7 days post-transplant, demonstrated NAC intolerance, received a multi-organ transplant, or previously received a liver transplant. Patients meeting inclusion criteria were divided into those who received the NAC protocol (exposure group) and those who did not (control group). The primary outcome was the incidence of EAD as measured by changes in bilirubin, AST, ALT, or INR through post-operative day (POD) 7. Secondary outcomes included graft nonfunction by POD 7, changes in renal function by POD 7, and intraoperative blood product requirements. Results: Of the 126 patients screened, 108 patients were included, with 47 in the exposure group and 61 in the control. On average, patients were 56.5 years old, 50% male, had a MELD 3.0 score of 21.9 with alcoholic cirrhosis being the most common indication for transplant. There was no difference between groups regarding the incidence of EAD (p=0.514). For secondary outcomes, NAC resulted in a statistically significant decrease in the incidence of primary graft nonfunction by POD 7 (p=0.035). All other secondary outcomes were not significantly different, including AKI (p=0.686), eGFR change (p=0.355), and intraoperative blood requirements (p=0.452). Conclusions: This retrospective study revealed no difference in EAD between the NAC and control groups, but did find a significant reduction in primary graft nonfunction at 7 days.