In this work, the combined influence of barium sulfate content and co-monomer concentration on the properties of acrylic bone cement for percutaneous vertebroplasty (PVP) was investigated using a response surface methodology. Cements were prepared with methyl methacrylate (MMA) and either diethyl amino ethyl methacrylate (DEAEM) or dimethyl amino ethyl methacrylate (DMAEM) as co-monomer in the liquid phase, while variable amounts of barium sulfate were incorporated to the solid phase in order to improve the radiopacity of cements. It was found that various properties such as peak temperature, setting time, residual monomer content, mechanical properties and injectability, had an effect on the occurrence of interactions (combined effect) between the barium sulfate and DEAEM in bone cements formulations when independent variables were at their maximum.