Early-onset hospital-acquired pneumonia (E-HAP) is one of the leading causes of sepsis and mortality after liver transplantation (LT). The appropriate antimicrobial therapy is crucially important for surviving sepsis in this context. The aim of this study was to analyze microbiological findings, associated factors, and optimal antibiotic regimens for E-HAP after LT. Patients demonstrating E-HAP in a single-center cohort of 148 LT recipients were prospectively detected. The diagnosis of pneumonia relied on a combination of supportive clinical findings and a positive culture of a lower respiratory tract sample. E-HAP was considered present if pneumonia occurred within 6 days of intensive care unit (ICU) admission after LT. Twenty-three patients (15.5%) developed E-HAP, which were caused by 36 pathogens (61.1% were gram-negative bacilli, and 33.3% were classified as hospital-acquired). For patients who developed E-HAP, the duration of mechanical ventilation and the ICU stay were significantly longer. Despite a trend toward higher mortality at any time in the E-HAP group, there was no significant difference in mortality between patients with E-HAP and patients without E-HAP. Lactatemia, vasopressor requirements, Simplified Acute Physiology Score II (SAPS II) score on ICU admission, and mechanical ventilation lasting more than 48 hours after LT were associated with E-HAP. Combinations of broad-spectrum b-lactams and aminoglycosides were active against more than 91% of the encountered pathogens. However, antibiotic de-escalation was possible in more than one-third of cases after identification of the pathogens. In conclusion, E-HAP after LT is a severe condition that appears to be influenced by physiological derangements induced by the surgery, such as lactatemia, vasopressor requirements, and mechanical ventilation requirements, as well as the postoperative SAPS II score. At the time of treatment initiation, an antimicrobial regimen usually proposed for late-onset pneumonia should be followed. Orthotopic liver transplantation (LT) is a widely accepted treatment for patients with end-stage liver disease. Despite global improvements in survival over the last few decades, sepsis remains the leading cause of early postoperative mortality. 1,2 Lower respiratory tract infections are a major concern in this context.