In a prospective study conducted in the Institute of Postgraduate Medicine & Research (IPGMR), Dhaka, 212 patients with prolonged pyrexia were thoroughly evaluated clinically and with the help of laboratory investigations with a view to reaching the diagnosis. Their clinical and laboratory data were recorded. Clinical features pertaining to a particular organ gave appropriate clue in 52% cases. Imaging techniques were instrumental in 24%, microbiological or serological investigations in 35%, invasive procedures were diagnostic in 42%, laparotomy had to be resorted to in five cases. Infectious diseases were the commonest causes of prolonged pyrexia accounting for about 63.21% of cases followed by neoplasms (12.74%) and connective tissue disorders (10.85%). Tuberculosis was the most common infection (24.53% of all cases) followed by enteric fever (12.74%) and visceral leishmaniasis (9.43%). Pleura was the commonest seat for tuberculosis followed by lymph nodes and abdomen. Leukemias were the commonest neoplasm and SLE the commonest connective tissue disorder presenting with prolonged fever. Several fundamental observations were made in the study. Infections are the commonest cause of prolonged fever in our community, neoplasms and connective tissue disorders are also not rare. Secondly, patients with temperature between 100 to 101 degrees F should not be denied evaluation with the apprehension of unnecessarily investigating for habitual hyperthermia, as the condition was distinctly rare in the series. Thirdly, analysis of materials from organs or systems suspected to be abnormal clinically or by simple imaging techniques had high diagnostic yield. Finally, usual causes of prolonged fever are illnesses ordinarily encountered in clinical practice, pyrexia becomes protracted either because the presentation is atypical or incomplete, or because we fail to make proper use of available clinical or paraclinical information.