Cirrhosis is known to be an important prognostic factor in determining morbidity and mortality in preoperative cardiac risk assessment for cardiac surgery. Data is limited on outcomes in patients with infective endocarditis (IE) and comorbid liver cirrhosis. The objective of our study is to evaluate the clinical outcomes in patients suffering from IE both with and without underlying liver cirrhosis as well as to determine rates of in-hospital mortality and factors that contribute to this outcome. Liver cirrhosis worsens clinical outcomes in patients with IE. Patients with a principal diagnosis of IE with and without liver cirrhosis were identified by querying the Healthcare Cost and Utilization (HCUP) database, specifically the National Inpatient Sample for the years 2013 and 2014 using International Classification of Diseases, Ninth Revision (ICD-9) codes. During 2013 and 2014, a total of 17,952 patients were admitted with a diagnosis of IE, out of whom 780 had concurrent liver cirrhosis. There was increased in-hospital mortality [15.6% vs 10.2%, aOR = 1.57 (1.27-1.93)], acute kidney injury [41.4% vs 32.6%, aOR = 1.45 (1.24-1.69)], and hematologic complications [32.1 vs 14.7%, aOR = 2.87 (2.44-3.37)] in patients with IE with liver cirrhosis when compared to patients with IE without liver cirrhosis. Patients having IE without liver cirrhosis underwent an increased number of interventions, i.e. aortic (7.2 vs 3.7%, aOR = 0.51 (0.34-0.76)) and mitral (4.9% vs 3.4%, aOR = 0.39 (0.23-0.69)) valvular replacements as compared to those with liver cirrhosis, which may explain the increased mortality seen in patients with liver cirrhosis. Liver cirrhosis is an important prognostic risk factor for in-hospital mortality in patients with IE. The coagulopathic state in addition to increased rates of bleeding complications and renal dysfunction make these patients poor surgical candidates thus contributing to higher mortality. Further research into the individual risk factors contributing to the increased mortality rates in patients with IE and cirrhosis is required.