Abstract Background Advancements in medical technology and increased life expectancy have been described as contributing to the evolution of endocarditis. We sought to determine whether there has been a change in the incidence, demographics, microbiology, complications, and outcomes of infective endocarditis over a 10-year time span. Methods We screened 28,420 transthoracic and transesophageal echocardiogram reports performed at the Gill Heart Institute for the following indications: fever, masses, emboli (including stroke), sepsis, bacteremia, and endocarditis in 2 time periods: 1999 to 2000 and 2009 to 2010. Data were collected from diagnosed endocarditis cases. Results Overall, 143 cases of infective endocarditis were analyzed (48 in 1999-2000 and 95 in 2009-2010). The endocarditis incidence per number of admissions remained nearly constant at 0.113% for 1999-2000 and 0.148% for 2009-2010 (P = .153). However, tricuspid valve involvement increased markedly from 6% to 36% (P < .001). Also, reported history of intravenous drug use increased from 15% to 40% (P = .002). Valvular complications doubled from 17% to 35% (P = .031). Septic pulmonary emboli increased from 10% to 25% (P = .047). Despite these noted differences, inpatient mortality remained unchanged at 25% and 28% (P = .696) for the 2 time periods, respectively. Conclusions The incidence of endocarditis at the University of Kentucky Medical Center has not changed and mortality remains high, but the “face of endocarditis” in Kentucky has evolved with an increased incidence of tricuspid valve involvement, valvular complications, and embolic events.