The propensity of immigrants to become self-employed has been widely studied in the ethnic and immigrant entrepreneurship literature (Light, 1972; Aldrich and Waldinger, 1990; Basu and Altinay, 2002; Levie, 2007). The majority of findings in this field come from qualitative studies on inter-group differences in the entrepreneurial activity, conducted in a reduced number of countries (such as the USA, Canada, UK, Australia, Germany and the Netherlands). However, a lack of economic and cross-section studies (Rath, 2000) analyzing the influence of individual attributes on the decision to start-up a firm is detected. Drawing on human capital and location economy theories, this study aims to fill this gap by conducting an empirical test of the effect of being an immigrant on the individual’s decision to create a company and by comparing the determinants of self-employment for immigrants versus natives in Spain. In particular, we pose the following questions: Are immigrants more likely to become entrepreneurs than natives? Which are the determinants of self-employment for both groups? Are there inter-group differences in the entrepreneurial choice among immigrants coming from different origins? Are there regional level differences in the self-employment of immigrants and natives in Spain?