A semiconductor structure having a hybrid crystal orientation is provided. The semiconductor structure includes an insulator layer, e.g., a buried oxide (BOX), on a first semiconductor layer, and a second semiconductor layer on the buried oxide, wherein the first and second semiconductor layers have a first and a second crystal orientation, respectively. A first region of the second semiconductor layer is replaced with an epitaxially grown layer of the first semiconductor layer, thereby providing a substrate having a first region with a first crystal orientation and a second region with a second crystal orientation. An isolation structure is formed to isolate the first and second regions. Thereafter, NMOS and PMOS transistors may be formed on the substrate in the region having the crystal orientation that is the most appropriate.