Implant provisional restorations should ideally be nontoxic to the contacting and adjacent tissues, create anatomical and biophysiological stability, and establish a soft tissue seal through interactions between prosthesis, soft tissue, and alveolar bone. However, there is a lack of robust, systematic, and fundamental data to inform clinical decision making. Here we systematically explored the biocompatibility of fibroblasts and osteoblasts in direct contact with, or close proximity to, provisional restoration materials. Human gingival fibroblasts and osteoblasts were cultured on the “contact” effect and around the “proximity” effect with various provisional materials: bis-acrylic, composite, self-curing acrylic, and milled acrylic, with titanium alloy as a bioinert control. The number of fibroblasts and osteoblasts surviving and attaching to and around the materials varied considerably depending on the material, with milled acrylic the most biocompatible and similar to titanium alloy, followed by self-curing acrylic and little to no attachment on or around bis-acrylic and composite materials. Milled and self-curing acrylics similarly favored subsequent cellular proliferation and physiological functions such as collagen production in fibroblasts and alkaline phosphatase activity in osteoblasts. Neither fibroblasts nor osteoblasts showed a functional phenotype when cultured with bis-acrylic or composite. By calculating a biocompatibility index for each material, we established that fibroblasts were more resistant to the cytotoxicity induced by most materials in direct contact, however, the osteoblasts were more resistant when the materials were in close proximity. In conclusion, there was a wide variation in the cytotoxicity of implant provisional restoration materials ranging from lethal and tolerant to near inert, and this cytotoxicity may be received differently between the different cell types and depending on their physical interrelationships.