The purpose of this work was to develop a meaningful in vitro dissolution method for evacetrapib spray-dried dispersion (SDD) tablets that is discriminating for crystalline drug substance (DS) content. Justification of the method conditions included evaluation of dissolution media, rotation speed, surfactant selection and level of surfactant to achieve sink conditions. Discrimination was illustrated by testing SDD tablets spiked with 10%, 20%, and 30% crystalline DS. The results demonstrated a 13%, 22% and 32% drop in the dissolution end point, respectively, as compared to unspiked SDD tablets. Additionally, tablets containing crystalline DS and tablets containing SDD were tested in a relative bioavailability (RBA) study. Utilizing the proposed dissolution method, the dissolution end point of SDD tablets was determined to be approximately 4 fold higher than that of the tablets containing crystalline DS. These results compare favourably to the in vivo RBA study results where SDD tablets had a 4.6 fold increase in exposure compared to tablets containing crystalline DS.