Direct reprogramming of somatic cells to pluripotent stem cells entails the obliteration of somatic cell memory and the reestablishment of epigenetic events. Induced pluripotent stem (iPS) cells have been created by reprogramming somatic cells through the transduction of reprogramming factors. During cell reprogramming, female somatic cells must overcome at least one more barrier than male somatic cells in order to enter a pluripotent state, as they must reactivate an inactive X chromosome (Xi). In this study, we investigated whether the sex of somatic cells affects reprogramming efficiency, differentiation potential, and the post-transcriptional processing of Xist RNA after reprogramming. There were no differences between male and female iPS cells with respect to reprogramming efficiency or their differentiation potential in vivo. However, reactivating Xi took longer than reactivating pluripotency-related genes. We also found that direct reprogramming leads to gender appropriate posttranscriptional reprogramming: like male embryonic stem (ES) cells, male iPS cells expressed only the long Xist isoform, whereas female iPS cells, like female ES cells, expressed both the long and short isoforms.