Background: One of the most common presenting symptoms patient presents to any medicine OPD is fever. This prospective study was conducted to find out the spectrum of diseases causing PUO in A Tertiary Care Hospital (in the eastern part of the country). Materials &Methods: This study was conducted at PEERLESS HOSPITAL & B. K. ROY RESEARCH CENTRE, KOLKATA, multi- Speciality state-of-art tertiary care hospital on 80 patients admitted over duration of one and half year duration of January 2013 to November 2014.A thorough history and standardized thorough physical examination followed by routine laboratory investigations such as complete haemogram, urine examination and culture, peripheral blood smear for malarial parasite, sugar, urea & creatinine, blood culture, chest x-ray, ultrasonography abdomen and dengue IgM,NS-1Ag was performed. Results: Infections diseases were major category of causes of PUO (48.75%),and was followed by autoimmune diseases (12.5%)and close to that were neoplastic diseases (11.25%).Tuberculosis (n=13,16.25%) dominated, in various forms as the both pulmonary and extra pulmonary, affecting central nervous system and lymph nodes specially. Other Major causes were Brucellosis and enteric fever. HIV is emerging as important cause of PUO.Autoimmune diseases constituted second major category of disease after infectious disease, among which Systemic lupus Erythematous was the most common (n=5,6.25%) followed by other diseases including MCTD, sarcoidosis, etc.Neoplastic Disease were among third more common disease with hematopoietic malignancies being the most common.Miscellaneous diseases found were hepatic abscess in 5 (6.25%), Thyroiditis in 2 (2.50%) and Hashimato's thyroiditis in 1 (1.25%). Total 66 patient (n=66, 82.5%) were diagnosed of total 80 patients. Out of 18 undiagnosed patients 3 patients remained afebrile on follow up for 3 months. Diagnosed patients were either treated or referred to other specialities. Conclusion: Infections remain the most important cause of PUO in India, confirming the trends found earlier in other studies. The incidence of Autoimmune diseases and neoplasms is nearly same. Tuberculosis remains most common cause among the all causes of PUO. Meticulous history taking followed by clinical examination is important to gain diagnostic clues and accordingly guiding diagnostic tools, and thereby ensuring judicious use of diagnostic tools in resource limited setting.