Abstract: Objective To compare the distribution of causes of fever of unknown origin(FUO) in its different courses. Methods Clinical data about FUO patients admitted to our department from October 2009 to December 2012 were retrospectively analyzed. The patients were divided into group A with its course of fever ≥ 21 days and group B with its course of fever ≥ 30 days. Results Of the 444 FUO patients enrolled in this study, 215(48.4%) were diagnosed with infectious diseases, 92(20.7%) were diagnosed with connective tissue diseases, 19(4.3%) were diagnosed with tumors, 35(7.9%) were diagnosed with miscellaneous diseases, and 83(18.7%) were not clearly diagnosed. The distribution of causes of FUO was similar in group A with its course of fever ≥ 21 days and group B with its course of fever ≥ 30 days. The incidence of infectious diseases, especially upper respiratory tract infectious diseases, was significantly lower in group B with its course of fever ≥ 30 days than in group A with its course of fever ≥ 21days(P=0.025 4,P=0.019 3). Conclusion No change occurs in the distribution of causes of FUO in FUO patients with their course of FUO ≥ 30 days, which is of certain clinical significance when upper respiratory tract infectious diseases with a tendency to cure are excluded.