Abstract Objectives Cefepime-induced neurotoxicity (CIN) has been demonstrated to be associated with cefepime plasma concentrations; however, the toxicity threshold remains unclear. The primary objective of this study was to identify the cefepime plasma trough concentration at which neurotoxicity occurs. Secondary objectives were to determine the incidence of CIN at a large tertiary institution and to identify patient factors associated with the development of CIN. Methods A retrospective review of all adult patients administered cefepime between October 2017 and May 2018 in a tertiary hospital was conducted to determine total incidence of CIN. A receiver operating characteristic (ROC) curve was constructed to review the sensitivity and specificity of using various cefepime trough plasma concentrations to predict the development of neurotoxicity. Cefepime plasma concentrations were measured using ultra-HPLC. A regression was conducted to identify patient factors associated with CIN. Results In total, 206 patients were administered 259 courses of cefepime, with an overall CIN incidence of 6% (16/259 courses). A total of 64 courses had a cefepime trough concentration measured (24.7%). A cefepime trough concentration of 36 mg/L provided the best differentiation between patients who experienced neurotoxicity and those who did not. No other patient covariates were identified to be significantly associated with neurotoxicity occurring. Conclusions A cefepime trough plasma concentration ≥36 mg/L appears to be the most sensitive and specific cut-off to predict CIN occurring. No patient factors were associated with the development of CIN when accounting for cefepime trough plasma concentrations.