In this research, the rapid expansion of acetaminophen with Supercritical Fluid (SCF) Carbon Dioxide (CO2) was studied. The purpose of this investigation was to examine the influence of process parameters in the particle size and morphology of the anti-inflammatory drug. The parameters studied include: temperature, pressure, flow rate, and depressurization rate. Variations were made to each parameter maintaining constant the others. The resulting particles were further analized by image analysis, and scaning electron microscopy (SEM) revealing that the crystalline nature of acetaminophen particles after expansion is mainly influenced by the manipulation of temperature and pressure (density effect). Different morphologies were obtained under various operating conditions and were further studied using calorimetric techniques.