Twin screw granulation (TSG) has been applied to wet granulation, although its application in melt granulation has been more limited. This work explores potential advantages of hot melt granulation using twin screw extrusion. Four main operating and formulation parameters were investigated: screw speed, number of mixing elements, temperature, and binder percentage. Combinations of these factors were then studied to determine their impact on the quantity and characteristics of granules within the desired size range of 125 – 1000 µm. A screening design of experiments (DOE) study was used with each factor set at three levels, to investigate individual factor effects and interactions. Two types of mixing elements were studied: kneading block (KB) and chaotic elements. The type and number of mixing elements were found to be paramount in contributing to the quantity and characteristics of granules formed. Results obtained agreed with previous findings in literature on the influence of different screw elements on the characteristics of granules formed by twin screw granulation. Additionally, the study revealed the unique impact which different mixer elements have on both granule production and characteristics. Depending on the specific need or use of granules in required applications, the granulation process can be effectively designed to meet the end product quality and outcome.