In order for the European Union (EU) to be successful in the global markets, higher education institutions (HEI) must be able to produce independent, creative, entrepreneurial individuals, who understand inter- and multidisciplinary challenges of the socio-economic environment and as a result can contribute to open innovation in true convergence with technological growth. EU’s success in the global competition is heavily dependent on the ability of the economy to produce digitally based innovative enterprises with high growth potential that can give stimulus to the actors of the socio-economic environment. Creating a common framework and a unified entrepreneurial ecosystem across the EU requires a core engine of open innovation and co-creation among all the involved stakeholders in order for the inequality among the regions of the EU to be decreased. Currently, EU significantly lacks such capacities of fostering digitally driven startups in true co-creation with all stakeholders. Such requirement not only that ensures long terms sustainability and societal development by improving living conditions, but it also drives the need for more innovation and knowledge exploitation. More innovation towards finding unique solutions to growth in a digitally driven quadruple helix context (university/innovation, startups/market, policy, society, investors/associations) where digital entrepreneurship (DEP) - in a quadruple helix co-creation- should be the key driver of regional and EU growth. To this end, iSTART responded to this need by aiming to develop an innovative, evidence based transnational framework that will markedly improve the knowledge and skills of academic institutions to produce more market/ startup oriented DEP curricula, reducing the barriers in this field. The project consortium comprised of key academics, investors, incubators from different sectors who co-created the envisaged DEP curriculum and piloted it through an open innovation and co-creation virtual learning environment (VLE). The outcome was directly pertinent to quadruple helix-academia co-operation for innovation and best practices with respect to DEP, and can also support policy reform in this area, leading to more prepared graduates ready for the startup market. In addition, iSTART enabled transnational DEP skill development/learning mobility leading to DEP homogeneity in EU towards targeting the common EU market. Overall, iSTART also followed up the recent plans of the EU to promote entrepreneurship and social cohesion as well as digitalization of higher education and of industries. This makes iSTART directly relevant to the current objectives of the participating organizations. Additionally, iSTART was aligned with the goals of Strategic Partnerships for academia-market-society collaboration/innovation, with the Headline Education Target, Entrepreneurship 2020, Startup Europe Initiative, and with the EU Higher Education Modernisation Agenda by providing incentives for higher education internationalization, market-oriented curriculum development, and co-creation with business through integrated features, that will lead on the long term to better involvement and support from the industry side to academia. Similarly, iSTART is in line with the European cooperation in education and training (ET2020) strategy by fostering life-long-learning, improving the quality of education through stakeholder engagement, and promoting creative thinking towards DEP. In order to achieve this mission, iSTART employed the following approach:O1) Training needs analysis identification (together with a benchmark of quadruple helix status/co-creation practices)O2) Two Trainers' labs (capitalization and peer development of the overall framework for iSTART) O3) DEP Curriculum & Virtual Learning Environment (VLE) platformO4) Four academies (curriculum piloting, DEP pitching, VLE testing - together with iSTART partners, students and quadruple helix stakeholders). The impact of iSTART, by developing a market oriented DEP curriculum, leading to more feasible digital startups, is to achieve this through co-creation in a blended and open innovation manner with quadruple helix stakeholders - through the developed VLE: 1) Transform European Higher Education & Research Institutes to Entrepreneurial Institutes 2) Transform higher education students to European Digital Entrepreneurs 3) Diversify & Europeanize Incubators’, Investors’ and high-tech companies’ portfolio and footprint4) Advance problem-solving capacities of European Local/Public communities under the patronage of the quadruple helix 5) Enhanced homogeneity of technology adoption and integration in quadruple-helix stakeholder related processes and teaching and learning (for higher education) 6) Enhancement of social stakeholder awareness/cohesion through the open VLE in relation to digital entrepreneurship practices 7) Expansion of the digital entrepreneurship trends within the EU.