Polyurethane foams are widely used in biomedical applications due to their desirable mechanical properties and biocompatibility. However, the cytotoxicity of its raw materials can limit their use in certain applications. In this study, a group of open-cell polyurethane foams were investigated for their cytotoxic properties as a function of the isocyanate index, a critical parameter in the synthesis of polyurethanes. The foams were synthesized using a variety of isocyanate indices and characterized for their chemical structure and cytotoxicity. This study indicates that the isocyanate index highly influences the chemical structure of polyurethane foams, also causing changes in cytotoxicity. These findings have important implications for designing and using polyurethane foams as composite matrices in biomedical applications, as careful consideration of the isocyanate index is necessary to ensure biocompatibility.