Purpose: To study the clinical characteristics of patients with definite fungal endocarditis (FE) aiming to detecte clinical predictors for early diagnosis. FE is a devastating disease that is associated with multiple morbidities and high mortality. Diagnosis is difficult and usually very late. Perhaps early diagnosis and treatment can result in better outcome.Method: Retrospective analytic study that included 232 patients with a definite IE in the period between February 2005 and September 2011. Results: 31 (13.3%) patients had FE. The whole group was relatively young with median age of 35 years (range: 13-74) in FE group and 28.5 years (range: 15-50) in non-FE group. In the FE group 22 cases had Aspergillus, 6 cases had Candida [71 % vs. 19.3 %, p< 0.001] and 3 had other fungi.Native RHD was less prevalent in FE group [3.2 % vs. 37.8%, p< 0.001; OR: 0.1, 95% CI = 0.04 – 0.49)]. The FE group had more cardiac prostheses [74.2% vs 23.8%, p<0.001; OR: 9.18, 95% CI = 3.8- 21.9)]. Early P.V.E. was more prevalent among FE group [64% vs. 38%, p=0.059], late P.V.E. was more common in non-FE [61% vs. 36%, p=0.059]. Cardiac vegetations were more common in FE group than the non-FE group [100% vs. 84.6%, p=0.002]. Vegetations in FE group were larger than the non-FE group [20 mm vs. 12 mm, p=0.002].Negative blood Cultures were more common among FE group [80.6% vs. 52%, p=0.003]. HAI(identified as :infection contracted ≥ 48 hours after hospital admission, infection appearing within: a) 1 month of receiving IV cannulation, chemotherapy or dialysis; b) 3 months of admission into an acute care facility, c) any time of admission to a nursing home) was significantly more common in FE group [90.3% vs. 58.2%, p=0.001; OR: 6.7, 95% CI= 1.98 -22.9)].Complications were high in both groups, however death was significantly higher in FE [(54.8%) vs. 66(32.8%), p=0.017].Through multivariate logistic regression test, the following variables were independently associated with FE: prosthetic cardiac valves [OR: 14, 95% CI: 5 to 41, p<0.001], HAI [OR: 8, 95% CI: 2 to 29, p=0. 003], absence of splenomegaly [OR: 0.174, 95% CI: 0.034 to 0.879, p=0. 034] and IVDU [OR: 12, 95% CI: 2 to 64, p=0. 004]. Conclusion: Looking for clinical characteristics might help in the diagnosis of FE which is a disease associated with negative blood culture and grave prognosis. The association of prosthetic cardiac valves, HAI, large vegetation, IVDU and absence of splenomegaly in a culture negative IE might help this diagnosis.