Peripheral cities are more susceptible to transportation infrastructure than core cities in terms of entrepreneurial activities. We use market access approach to estimate the impacts of highways and high-speed railways on entrepreneurship in the small and medium-sized cities in China under knowledge spillover entrepreneurship framework. The results show that the increased market potential caused by highways and high-speed railways significantly improves the entrepreneurial performance of peripheral cities. The entrepreneurship effects of highways are stronger than high-speed railways, especially for these cities that are relatively closer to core cities. On the contrary, the entrepreneurship effects of high-speed railways are stronger in these cities that are far from core cities. This study suggests that transportation infrastructure plays an important role in entrepreneurship, and there is a complementary effect between highways and high-speed railways.