Introduction: Acute febrile illness with Multi Organ Dysfunction Syndrome (MODS) carries significant morbidity and mortality despite standard therapy in intensive care settings. Infections are the most common cause of MODS followed by polytrauma. Present study was undertaken in medical intensive care units of a tertiary hospital to study the aetiology and outcome among patients with acute febrile illness developing MODS. Aim: 1) To study the aetiology of acute febrile illness in patients developing MODS. 2) To study the final outcome among these patients. Materials and Methods: The present study was conducted at a tertiary care hospital in Mysuru, Karnataka, India, over a period of 6 months from July 2013 to December 2013. The Institutional Ethics Committee Approval (IEC) was obtained before the commencement of the study. A total of 213 cases admitted in intensive care unit with acute febrile illness with two or more organ dysfunction were screened for the inclusion and exclusion criterias. Results: A total of 213 cases of acute febrile illness with one or more organ dysfunction were screened. Of the screened patients 75 patients were finally included in the study out of which 46 (61.3%) patients were males and 29 (38.7%) patients were females. Aetiology for acute febrile illness with MODS could be established in 49 (65.3%) patients and it was obscure in 26 (34.7%) patients despite repeated investigations. Dengue infection (29.3%) was the commonest cause of febrile illness with MODS followed by leptospirosis (22.7%). Majority of these patients had haematological derangements (78.7%) and liver function test abnormalities (68%). Out of these 75 cases, 54 (72%) patients recovered completely and 21 (28%) patients died. Among males (N=46), 35 (76.1%) patients recovered and 11 (23.9%) patients died where as among females (N=29), 19 (65.5%) patients recovered and 10 (34.5%) patients died. Mortality was proportionate with the number of organ dysfunction, especially Central Nervous System (CNS) involvement. Conclusion: Incidence of febrile illness with MODS is more prevalent in males but the outcome appears poorer among females. The diagnosis remained obscure in a sizable proportion of these patients. Prognosis was inversely dependent on the number of organs involved especially with CNS manifestations.