Abstract: Background: Infective endocarditis (IE) is associated with high inhospital mortality. New microbiological diagnostic techniques have reduced the proportion of patients without etiological diagnosis, but in a significant number of patients the cause is still unknown. Our aimwas to study the association of the absence of microbiological diagnosis with in-hospital prognosis. Methods: Prospective cohort of 2000 consecutive patients with IE. Data were collected in 26 Spanish hospitals. Modified Duke criteria were used to diagnose patients with suspected IE. Results: A total of 290 patients (14.8%) had negative blood cultures. Etiological diagnosis was achievedwith other methods (polymerase chain reaction, serology and other cultures) in 121 (6.1%). Finally, therewere 175 patients (8.8%)without microbiological diagnosis (Group A) and 1825with diagnosis (Group B). In-hospital mortality occurred in 58 patients inGroup A (33.1%) vs. 487 (26.7%) inGroup B, p=0.07. Patients inGroup A had a lower risk profile than those in Group B,with less comorbidity (Charlson index 1.9±2.0 vs. 2.3±2.1, p=0.03) and lower surgical risk (EuroSCORE 23.6±21.8 vs. 29.6±25.2, p=0.02). However they presented heart failure more frequently (53% vs. 40%, p=0.005).Multivariate analysis showed that the absence of microbiological diagnosis was an independent predictor of inhospital mortality (odds ratio 1.8, 95% Confidence Interval 1.1?2.9, p = 0.016). Conclusion: Approximately 9% of patients with IE had no microbiological diagnosis. Absence of microbiological diagnosis was an independent predictor of inhospital mortality.

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