Aim: The study involved design of experiment guided discriminatory dissolution method development for poorly soluble, ezetimibe tablets. Objective: In the current scope of study, ezetimibe tablets are selected as a suitable drug product candidate to evaluate the application of design of experiments in discriminatory dissolution method development for poorly soluble drug. Ezetimibe is practically insoluble in all the aqueous buffers. Methodology: 2-Level factorial design is selected as suitable model to build the experimental setup. Different factors like pH of dissolution media, sodium lauryl sulphate concentration, dissolution media volume and agitation speed (RPM) are selected for the study and dissolution % release at 5, 10, 15, 20, 45 min and % RSD of dissolution values at 20 min were selected as responses based on prior experience. The responses are evaluated for statistical significance and for adequacy of the built design with the help of different tools like ANOVA and diagnostic graphs. Results: It is observed that pH of dissolution media, surfactant concentration are having minimal positive effect on all of the responses. Whereas agitation speed and dissolution media volume were having significant positive effect on all responses, except for % RSD at 20 min and is inversely proportional to agitation speed. Conclusion: With the current scope of study design of experiments as an effective tool for discriminatory dissolution method development is employed to prove adequacy. Selected solutions from predictions were executed for experimental results and were compared against predictions to validate model.