OBJECTIVE To investigate the etiology and clinical features of fever of unknown origin (FUO). METHODS The clinical data including etiology, diagnostic approaches, and clinical features were retrospectively analyzed in 816 patients with FUO who were presented in our department from January 2000 to January 2009. RESULTS Of these 816 FUO cases, 766 (93.9%) were confirmed to be with infective diseases(40.4%, n=330), connective tissue diseases (34.4%, n=281), malignant tumors (10.9%, n=89), other known diseases (8.1%, n=66), and unknown diseases (6.1%, n=50). The most common infective disease was tuberculosis (49.7%, 164/330), the most common connective tissue disease was adult-onset Stills disease (AOSD)(55.2%, 155/281), the most common malignant tumor was lymphoma(56.2%, 50/89), and the most common "other known disease" was Crohns disease(22.7%, 15/66). All lung cancer cases had obstructive pneumonia. Significantly more elderly patients suffered from infective diseases (49.4% vs.32.0%) and malignant tumor (15.6% vs. 6.4%) compared with the non-elderly (both P=0.0000), while the proportion of connective tissue diseases was significantly less than that of the non-elderly (17.9% vs. 50.1%, P=0.0000). CONCLUSIONS Most FUO can be confirmed after careful examinations and analysis. The main cause of FUO is infective diseases, especially tuberculosis in the elderly. The connective tissue diseases and malignant tumors are also important causes.