Induced pluripotent stem (iPS) cells have recently emerged as a promising alternative to embryonic stem (ES) cells for modeling disease and developing therapeutics. It is important to explore the differences between these two cell types to pinpoint genetic abnormalities or discover if they have a tendency to differentiate toward a particular cell type. Here, we report an experimental protocol based on embryonic development that produces large numbers of endothelial cells—the cells that line the interior surface of blood vessels—derived from multiple human ES cells or iPS cells. The steps involved in this protocol resulted in an expanding, uniform pool of cells that in all functional aspects were similar to endothelial cells. Comparison of the various kinds of RNA in the cells revealed limited gene expression variability between multiple lines of human iPS–derived endothelial cells, or between lines of ES– and iPS–derived endothelial cells. These results demonstrate a method to generate large numbers of pure human endothelial cell progenitors and differentiated endothelial cells from pluripotent stem cells, and suggest individual lineages derived from human ES and iPS cells may have low variance at the level of gene expression. Given the limited variability, endothelial cells derived from patient-specific iPS cells may prove useful in modeling diseases of the blood vessels or in testing potential new drugs to treat these diseases.