After more than ten years of development, the H-II Transfer Vehicle (HTV), a space station cargo transfer spacecraft, successfully docked with the International Space Station on September 18, 2009. The HTV is an inter-orbit cargo transfer spacecraft that carries both pressurized cargo and unpressurized cargo exposed to space. The vehicle is equipped with the crew specifications necessary for astronauts to unload pressurized cargo, and is the first spacecraft other than the space shuttles to transport unpressurized cargo. This paper describes the safety design for crew activities particular to the HTV, newly developed technologies that enable cargo shipment, and the general details of the development, which was carried out under the policy of adopting flight-proven technologies to enhance the reliability and safety of a mission.