The orthotopic liver transplant (OLT) population has been particularly affected by the increase in vancomycin-resistant enterococcus (VRE) infections in recent years. Pre-transplant colonization prevalence, the role of spontaneous bacterial peritonitis (SBP) antimicrobial prophylaxis as a risk factor, and the risk of post-OLT infection in colonized patients are all unknowns. We prospectively evaluated OLT candidates at our center with the aim of answering these questions. Vancomycin-resistant enterococcus colonization status was determined by rectal culture. Data collected included illness severity, antibiotic use (including SBP prophylaxis), waiting time, previous hospitalizations, and invasive procedures. Eighty-eight patients (31 female, 57 male, median age 52 years) were enrolled. The most common diagnoses were hepatitis C (49%), primary sclerosing cholangitis (13.6%), and alcoholic liver disease. Median MELD score was 11.5 (range 7–24), and median waiting time was 551 days (range 1–2224). Vancomycin-resistant enterococcus risk factors were common in our patients: recent hospitalization in 16%, recent antibiotic exposure in 39%, and renal insufficiency in 7%. Seventeen percent were receiving SBP prophylaxis. Despite the presence of established risk factors, VRE colonization prevalence was 3.4%. Preliminary limited data showed poor correlation between screening rectal cultures and operative/peri-operative cultures. Vancomycin-resistant enterococcus colonization prevalence in an OLT candidate population with mid-level MELD scores was low, and SBP prophylaxis was not a significant risk factor.