UEFI Boot a NTFS Drive

The latest version of Rufus allows seamless UEFI boot from an NTFS partition.

If you select a Windows installation ISO, set the partition scheme to GPT partition scheme for UEFI computers and also set the file system to NTFS, Rufus will add everything required to allow booting NTFS partition from an UEFI system.

Outside of using Windows installation media, you can also create a "blank" NTFS bootable UEFI drive when running Rufus in advanced mode (enabled by clicking the while triangle near Format Options) by selecting UEFI:NTFS as the boot option. In this case, you will just have to copy an /efi/boot/bootx64.efi or /efi/boot/bootia32.efi on the NTFS partition for your system to boot from NTFS.

The way it works is by adding a small (256KB) FAT partition at the end of the drive that contains am EFI executable that loads a Free Software (GPLv3) NTFS EFI driver and hands over the boot to the regular EFI bootloader on NTFS partition. This allows the installation of Windows media that contain an install.wim larger than 4GB and other stuff...

For more on this see the UEFI:NTFS project on github.

[Disclaimer: I am the author of Rufus and UEFI:NTFS]

From the Wikipedia article on UEFI:

The UEFI specification explicitly requires support for FAT32 for system partitions, and FAT12/FAT16 for removable media; specific implementations may support other file systems.

Personally I've yet to encounter any motherboard manufacturer who has implemented NTFS boot support in their UEFI modules.

Update: As mentioned in the comments below, two years after I posted the above there are now at least a few motherboards available with UEFI NTFS modules.