Fever of unknown origin (FUO) is a frequently observed phenomenon in clinical practice. The present study was aimed to investigate potential causes of FUO, thereby improving clinical diagnosis of this disorder.In this retrospective study, clinical data were collected from 215 patients who were diagnosed with FUO between January 2009 and December 2010, and an 18 to 36 months follow-up visit was also performed for these patients.Among these FUO cases, the most common causes of the disease were infectious diseases (IDs) (42.3%), followed by connective tissue diseases (CTDs) (32.1%), miscellaneous (Mi) (10.7%) and neoplasm (N) (6.5%), while the causes for the other 18 cases (8.4%) were still unknown. The most common types of ID, CTD, and N were tuberculosis (16/91, 17.6%), adult onset Still disease (AOSD) (37/69, 53.6%) and non-Hodgkin lymphoma (6/14, 42.9%), respectively.IDs still represent the most common causes of FUO. Regularly intermittent fever with urinary infections and irregularly intermittent fever with infective endocarditis may be regarded as some signs in clinical diagnosis of FUO.