The aim of this study was to evaluate the accuracy of procalcitonin (PCT) in predicting infective endocarditis (IE). 23 adult patients with IE, 30 patients with sepsis and 30 with tick-borne encephalitis were included in this prospective study. The PCT serum level, C-reactive protein (CRP), total leukocyte, and immature polymorphonuclear (PMN) cell counts were determined on admission, prior to the institution of antibiotic therapy, and compared according to the diagnosis. The median PCT level in patients with IE endocarditis was 0.81 ng/ml, in patients with sepsis it was 43.74 ng/ml, and in the group with viral infection it was 0.25 ng/ml (P < 0.001). The highest PCT level was found in patients with Staphylococcus aureus endocarditis. The area under the receiver operating characteristic curve that used PCT to predict IE was 0.722 (95% CI 0.572-0.873), compared with 0.909 (95% CI 0.829-0.989) for CRP, 0.699 (95% CI 0.551-0.846) for immature PMN cell count, and 0.619 (95% CI 0.468-0.770) for leukocyte count. Our study fails to demonstrate superiority of PCT as a diagnostic laboratorial parameter in predicting IE compared to CRP.