High-impact companies are a very important source of economic and job growth. Identifying the drivers and barriers behind their development is key to developing a sound supporting policy framework. The Global Entrepreneurship Development Index (GEDI) can interpret and measure entrepreneurial capacity as a systemic phenomenon. For that reason it provides a powerful means of assessing regional entrepreneurial performance. This paper begins by analyzing GEDI results in order to draw a picture of how well entrepreneurship systems perform in Latin America and the Caribbean (LAC). The lessons drawn from this analysis are deepened through the qualitative analysis of nine case studies on the creation and development of successful high-impact companies in the region.