Significance It is well recognized that several chemicals and/or drugs are potentially harmful if used during pregnancy. Unfortunately, systems capable of predicting which drugs affect embryonic development rely almost exclusively on prenatal animal testing, with all the associated limitations. Using human pluripotent stem cells, we developed a fully humanized system capable of predicting which drugs affect, specifically, vascular embryonic development. The system was used to screen a library of chemicals (1,280 drugs), and two compounds were identified as specific inhibitors of human embryonic vasculature. The platform described here is a valid alternative to animal testing and can be used to screen existing and newly developed drugs.