Clopidogrel hydrogen sulfate is a famous antiplatelet agent for vascular disease. FormsI and II can be used as medicine. However, both forms exhibit low density and flowability. In addition, formI shows low polymorph stability. To solve these problems, spherical crystallization technologies were developed for the two forms. For formI, the mechanism was studied and turned out to be 2D nucleation and spherulitic crystal growth. In case of formII, the spherical crystallization process was based on agglomeration. The influence of temperature, acid, and crystal seed were investigated. The optimized spherical formsI and II showed much higher density and flowability as well as high polymorph stability.