Entrepreneurial universities are a significant element of entrepreneurial ecosystems and aspire to foster entrepreneurial initiative through their "third mission". However, while entrepreneurial ecosystems are scrutinized using a contextual approach to detect differences and similarities and how they affect entrepreneurship, little is known about how entrepreneurial universities impact entrepreneurial initiatives in general, considering multiple environments. Drawing on entrepreneurial university and entrepreneurial ecosystem theories, a conceptual framework is proposed that aims to explain the effect of the entrepreneurial university on an entrepreneurial initiative through its three "missions", using an entrepreneurial ecosystem taxonomy. Based on individual data from the Global Entrepreneurship Monitor, this entrepreneurial initiative analyzed 18 European countries in 2017. The results do not generally support the importance of entrepreneurial universities to entrepreneurial initiative. The relevance of entrepreneurial universities increases in more fragile entrepreneurial ecosystems since individuals need support over multiple dimensions. Conversely, the entrepreneurial universities that are embedded in stronger entrepreneurial ecosystems lose relevance and negatively affect the entrepreneurial initiative. Therefore, the value of entrepreneurial universities is reduced when individuals receive greater support from other dimensions. The variations across both groups suggest that the concept of entrepreneurial universities is not a contemporaneous phenomenon; however, their effect is progressively revealed by the maturity of each university's mission. This perspective substantially changes the understanding of entrepreneurial universities as a thwartwise strategy, suggesting that the universities' impact is expanded as their missions gradually evolve. Overall, the study contributes to an understanding of the implications for universities that blindly follow entrepreneurship, neglecting the exogenous environment, namely, the entrepreneurial ecosystem and individual drive.