Infective endocarditis (IE) is still a significant cause of mortality in European hospitals, despite of the fact, that large nationwide studies were performed in last twenty years and pathogens are well known. The aim of the study was to assess risk factors, mortality, etiology and proportion of elderly patients within a longitudinal nation wide survey of infectious endocarditis in Slovakia. Etiology, risk factors and outcome of 1003 cases of infective endocarditis (IE) in Slovakia over the last 33 years have been assessed. The majority of IE were caused by Staphylococci (28.3%), 15.6% were due to Viridans streptococci, 10% due to Enterococci, 8.2% by gram-negative bacteria, Acinetobacter baumannii and Pseudomonas aeruginosa, 3.7% by other organisms and 31.0% of all cases were culture negative. The following risk factors were recorded: age > 65 (36.8%), rheumatic fever (15.3%), dental surgery (8.7%), previous non-cardiological surgery (8.2 %), neoplasia (8.1%), diabetes (7.8%), any endoscopy (8.5%) and dialysis (4.6%). All patients were treated with antimicrobials, 507 (51%) also with surgery. Survival rate at day 60 after diagnosis was 88.1% (n=883). Only age >65 (34.3% vs. 49.5%, p=0.045) and persistent bacteremia (with three or more positive blood cultures 15.7% vs. 34.5%, p=0,001) were significantly associated with higher attributable mortality. Concerning risk factors, etiology and therapeutic strategies, rheumatic fever and neoplasia showed decrease in tendency. Dental surgery and tonsillitis were less frequent as well (26.7% vs. 2%, p<0,001 and 16% vs. 1%, p<0.001). There was a significant shift in etiology after 1997: culture-negative endocarditis was surprisingly more frequently observed in the 2007-2017 period than before and represented 10.7% of all cases in 1984-1990 in comparison to 25.1-25.6% in 2007-2010 and 2011-2017. Staphylococci decreased from 48% to 29.6% (2007-2017), but are still major pathogens. Persistent bacteremia (3 or more positive blood cultures 5.3% vs. 24.7%, p<0,001) was less commonly observed within the 1st period (1984-1990) in comparison to 2007-2010. More patients in the 1st period (1984-1990) had embolization complications of IE than in the fifth and sixth period (2007-2017) (76 vs. 16.3% p<0.001). CNS embolization decreased from 14% to less than 5% (p<0.003). Attributable mortality was lower too (26.7% vs. 9.5%, p<0.001) because of increased proportion of cardiac surgery in the treatment of IE in 2007-2017 in comparison to 1984-1990. Study has showed significant shifts in etiology, risk factors and complications over the observed time periods in Slovakia.