Given recent demands for more co-creational university technology commercialisation processes involving industry and end users, this paper adopts a micro-level approach to explore the challenges faced by universities when managing Quadruple Helix stakeholders within technology commercialisation processes. To explore this research question, a qualitative research methodology which relies upon comparative case analysis was adopted to explore the technology commercialisation process in two universities within a UK region. The findings revealed that university type impacts Quadruple Helix stakeholder salience and engagement and consequently university technology commercialisation activities and processes. This is important as recent European regional policy fails to account for contextual influences when promoting Quadruple Helix stakeholder relationships in co-creational university technology commercialisation.