Current protocols to differentiate human induced pluripotent stem cells (h-iPSCs) into endothelial cells (h-iECs) lack reliability. Here we describe a method for rapid, consistent and highly efficient generation of h-iECs from h-iPSCs. The protocol entails delivery of modified mRNA encoding the transcription factor ETV2 at the intermediate mesodermal stage of differentiation. This approach reproducibly differentiated thirteen diverse h-iPSC lines into h-iECs with exceedingly high efficiency. In contrast, differentiation with the standard protocol, which relies on endogenous ETV2, was inefficient and notably inconsistent. Our method generated h-iECs that were functionally competent in many respects, including ability to form perfused vascular networks in vivo. Importantly, timely activation of ETV2 was critical and bypassing the mesodermal stage produced putative h-iECs with reduced expansion potential and that lacked ability to form functional vessels. Our protocol could have broad application in regenerative medicine and reliably provide an unlimited number of autologous h-iECs for vascular therapies.