The purpose of this study was to investigate the precise effect and rank the importance of cavity preparation and restoration variables on human pulp vitality. Fiftythree Class V unexposed cavities were prepared and restored with calcium hydroxide/amalgam, resin-modified glass ionomer, zinc oxide-eugenol, resin composite, or zinc polycarboxylate materials. Pulp vitality was reduced by the remaining dentin thickness of the cavity preparations, whereas the other variables, including the type of restorative material, had little effect. Restorative materials cause minimal pulp damage in isolation; it is more important to minimize the removal of intact dentin to maintain the vitality of teeth.