Enterovirus 71 (EV71) is a major pathogen for severe hand, foot and mouth disease (HFMD). Development of vaccines against EV71 would be the most effective approach to prevent the EV71 outbreak. Research and development (R&D) of EV71 vaccine was carried out in several Asian countries. Currently three companies in mainland China have completed Phase III clinical trials of inactivated EV71 whole-virus vaccines, whereas the other two companies have completed Phase I clinical trials separately in Taiwan and in Singapore. Results from those clinical trials have indicated high safety and immunogenicity of EV71 vaccine. Protective efficacies were over 90% on EV71-associated HFMD and over 80% on other EV71-associated diseases. In this paper, we summarize the results from three EV71 vaccine Phase III clinical trials and discuss the challenges of incorporating EV71 vaccine into Expanded Program on Immunization (EPI) in countries with EV71 epidemics.