The main objective of the present investigations was to apply quality by design (QbD) approach for the development of Oral Dispersible tablet containing Sildenafil Aspirin Co-crystals. Critical ingredients and the process parameters are linked to the critical quality attributes of the well desired product. Variability is reduced by the product and the process understanding which leads to quality improvement, risk reduction and ultimately productivity enhancement. Sildenafil citrate is a well-known selective inhibitor of phosphodiesterase type 5 enzyme (PDE5) extensively used for the treatment of erectile dysfunction (ED). Sildenafil citrate is a BCS class II drug having a low aqueous solubility so co-crystallization with Aspirin is a method of choice to increase the solubility and to have the quicker onset of action by avoiding the first pass metabolism, an oral rapid mouth dissolving tablets had been prepared using Sildenafil Aspirin co-crystals. Fast dissolving tablets of Sildenafil Aspirin Cocrystals were designed, developed, optimized and characterized by using statically 32 factorial design in which two variables namely the concentration of crosspovidone and the concentration of SSG were at three levels (low, medium and high). The main interactive influences were tested using the statistical model. The response surface plots were generated by the software for analyzing the effects of the independent variables on the response. All the batches of the oral dispersible tablet were prepared by the direct compression method. The tablets were evaluated for Pre-compression parameters e.g. Bulk density, Tapped density, Angle of repose, Carr’s compressibility index and Hauser’s ratio and also post compression parameters like hardness, wetting time, drug content uniformity, friability, Thickness, Disintegration time & In vitro dissolution. The 32 full factorial design revealed that the amount of super disintegrants significantly affect the dependent variables disintegration time and wetting time.