This paper sets forth a model of knowledge-based regional development conceived as a set of multi-linear dynamics, based on alternative technological paradigms. Utilizing longitudinal data from a Swedish region, and international comparisons, four stages of development are identified: Inception, Implementation, Consolidation and Renewal. Innovation policy is created ‘bottom-up’ as an outcome of ‘collective entrepreneurship’ through collaboration among business, government and academic actors – the ‘triple helix’. The key event is the creation of an entrepreneurial university, whether from an existing academic base or a new foundation, which takes initiatives together with government and industry to create a support structure for firm formation and regional growth. The result of these initiatives is a self-sustaining dynamic in which the role of academia and government appears to recede as industrial actors come to the fore and a lineage of firms is created. Nevertheless, as one technological paradigm is exhausted and another one is needed as the base for new economic activity, the role of academia and government comes to the fore again in creating the conditions for the next wave of innovation.