Extant research suggests that the founder’s activities and interactions are considered pivotal in driving the opportunity recognition process leading to international new venture emergence. This paper aims to explore the opportunity recognition process and international new venture emergence in the context of university high-technology spin-offs that are internationally market driven from inception. University spin-offs (USOs) are defined as ‘new firms created to exploit commercially some knowledge, technology or research results developed within a university’ (Pirnay et al., Small Bus Econ 21:355–369, 2003). To address this inquiry, this study imports theory from the entrepreneurship literature on organizational emergence, opportunity recognition, effectuation and the principle of individual self-efficacy. Drawing on empirical case data from four case USOs from Denmark and Ireland, this paper finds that the inventor-founders are typically engaged in opportunity recognition processes that are characterized as creative, driven by scientific innovations. It is indicated that the process of USO emergence and continuous development involves activities and interactions similar to typical international new ventures. The scientific knowledge that created opportunities for the emergence of INV-USOs across our cases endorses the view that innovation and internationalization are strongly correlated. Insights are provided on inventor-founders’ entrepreneurial intention demonstrated through activities and interactions in the on-going processes of creating the USO. Findings further highlight that self-efficacy of the inventor-founder(s) and access to specific resources (means at hand) are salient determinants for international new ventures to materialize. The study concludes with a proposed conceptual framework for further research on the creation of INV-university spin-offs. Conclusions and implications are drawn at the end of the article.