Human induced pluripotent stem (iPS) cells have previously been derived from somatic cells using viral vectors that integrate transgenes into the genome. Genomic integration, however, can allow persistent leaky expression of the transgenes and can create insertional mutations, thus limiting the utility of these cells for both research and clinical applications. Here, we describe the derivation of human iPS cells free of vector and transgene sequences using non-integrating oriP/EBNA1-based episomal vectors. The resulting iPS cells are similar to human embryonic stem (ES) cells in both proliferative and developmental potential. These results demonstrate that reprogramming of human somatic cells does not require genomic integration or the continued presence of exogenous reprogramming factors, and removes one important obstacle to the clinical applications of these cells.