Background: Acute febrile illness is also called as Acute undifferentiated febrile illnesses (AUFIs) and cause considerable morbidity, mortality and economic burden specially in developing tropical nations. This study was conducted to study Clinical and microbiological profile of patients with acute febrile illness at a tertiary hospital. Material and Methods: A Hospital based Prospective Cross sectional study was carried out in consecutive cases of both sexes and all adults (age more than 15 years) admitted to medical wards with a history of fever less than 10 days and continued to have oral temperature above 37.50 c. Results: Out of the 230 patients satisfied the inclusion criteria, 119 were males and 111 were females. The hospital stay varied from 5 – 10 days and the median hospital stay was 5 days. The AUFI were more during the post monsoon and winter season. The spectrum of clinical profile observed in our study were in the order ofDengue, Enteric fever, Malaria, Typhoid followed by Scrub typhus, Leptospirosis and Chikungunya in 132 (56.2%), 67 (29.13%), 13 (5.53%), 7 (2.97%), 6 (2.55%), 5(2.17%) and 5 (2.13%) respectively. 5 among them had dual infection and suffered from Dengue and Enteric fever. Irrespective of the gender, patients start attending the hospital from the fourth day of fever. The mean affected age was 40.9 years. The presentation of fever was maximum on the fourth day and sixth day of fever. The presenting features were more once the duration of disease increases, even though the commonest were myalgia, headache and chills. None of the patients had any complications and they were discharged within a period of 5 – 10 days. Conclusion: The distribution of disease among the 230 cases were in the order of Dengue, Enteric fever, Malaria, Typhoid followed by Scrub typhus, Leptospirosis and Chikungunya.