Vascular networks are central to the functioning of most tissues. We use a two-cell approach to bioengineer human vascular networks in vivo. In our model, human blood-derived endothelial colony-forming cells are combined with human mesenchymal stem cells (MSCs) in a biocompatible hydrogel and injected subcutaneously into immunodeficient mice where they form an organized vascular network that joins with the mouse vasculature. This model is ideally suited for studies on the cellular and molecular mechanisms of human vascular network formation and for developing strategies to vascularize tissues.