Emtricitabine and Tenofovir disproxil fumarate belongs to class of anti-retroviral drugs known as nucleotide analogue reverse transcriptase inhibitors. The main objective of the present study is to formulate and evaluate an immediate release tablet of Emtricitabine and Tenofovir disproxil fumarate using different disintegrants. Preformulation studies were performed prior to compression. The tablets were compressed using microcrystalline cellulose, lactose, pregelatinized starch, croscarmellose sodium, talc, sodium starch glycolate, magnesium stearate and opadry II blue was used for coating the tablets. The fabricated tablets were evaluated for various micromeritic properties like bulk density, tapped density, compressibility index, Hausner’s ratio, angle of repose and post compression characteristics like thickness, hardness, friability, disintegration time and drug release. Croscarmellose sodium is found to be the better disintegrant when compared to sodium starch glycolate in the formulation of immediate release tablets of Emtricitabine and Tenofovir disproxil fumarate. Compared to the direct compression, wet granulation with pregelatinized starch as binder was found to be the best method of choice for formulation of these tablets. The absorbance of Emtricitabine and Tenofovir disproxil fumarate were screened in the UV region and the maximum absorbance was found to be 282 nm and 258nm respectively and this was used for HPLC analysis. The results of the present study indicates that, the prepared tablets of Emtricitabine and Tenofovir disproxil fumarate could perform therapeutically, with improved efficacy and better patient compliance like that of the marketed product.