This paper explores the relationship between entrepreneurship, measured by the number of new firms per million inhabitants, and modern economic growth in Spain between 1886 and 2000. Following Audretsch and Keilbach’s methodology, our analysis seems to confirm that entrepreneurship has had a positive and statistically significant effect on GDP per capita and labor productivity. This finding challenges the traditional view that the entrepreneurial factor has hindered the country’s economic growth. Additionally, using data on the size and legal form of start-up firms, our results suggest that neither characteristic has been an important driver of Spain’s long-term economic growth. However, we find that the impact of both variables differs depending on the years studied. To our knowledge, this study is the first attempt to test econometrically the long-term contribution of entrepreneurship to Spain’s economic growth.