Aim: To evaluate the reliability & diagnostic efficacy of pleural glucose, total protein, Lactate dehydrogenase(LDH), Adenosine Deaminase(ADA) and cholesterol in diagnosis of pleural effusion (PE) & to study clinical, biochemical & cytological markers which helps in establishing the exact diagnosis of different causes of pleural effusion. Materials and Methods: A Prospective observational-study done at Department of General Medicine of Govt. Medical College Haldwani over 2 years (2016 -2018) period. 122 patients above the age of 16 years with pleural effusion were included in our study. Thoracocentesis was done and an adequate amount of pleural fluid was aspirated to carry out the requisite tests. Results: The mean age of the studied patients was 44.72±17.3 years. 65.6% were males. Fever and cough were the commonest clinical findings. Sputum test for AFB was found positive only in 9.0% cases. Cytology of pleural fluid for malignant cells was found to be positive in 10.7% of the studied patients and 9.8% mortality rate due to pleural effusion was found. Conclusion: The most useful tool in establishing the exact diagnosis of PE was pleural fluid cytology and pleural fluid cell count.