Objectives: To assess the diagnostic utility of clinical features in the major diagnostic categories of Fever of unknown origin (FUO). Methods: One hundred and thirty-three patients meeting the classic criteria of FUO were included in the study. A structured diagnostic protocol was used in all cases. Sensitivity, specificity, positive and negative predictive values (PPV and NPVs), and likelihood ratios of positive and negative tests (LR+ and LR-) were estimated with 95% confidence intervals (95% CIs) for all clinical findings. Results: Clinical and epidemiologic features with best diagnostic utility indexes for the three major diagnostic categories were: weight loss of 15 pounds or more (