Easy2Boot can support many different filesystems, MBR-payloads, UEFI-payloads, Removable and Fixed Disks, etc.
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Use this 'Guide' to help you choose the best way to set up and use an E2B USB drive...
1. Type of E2B Drive (Fixed v. Removable USB drive)
When booting Windows-based payloads, it is important to know what type of USB drive you have.
Use RMPrepUSB to check if your USB drive is the Fixed type (e.g. USB Hard Disk) or Removable type (*recommended).
E2B is easier to use if the drive is the Removable USB type (e.g. for Windows ISOs), but you can use a USB HDD if you wish (but some changes may be required when booting Windows Install ISOs, see here).
Note that some USB Flash drives can be very slow (even some 'fast' USB 3.0 ones such as Lexar P20!). I highly recommend the SanDisk Cruzer Extreme USB 3.0 Removable USB drive for E2B - for larger sizes, speed and robustness, a cheap SSD HDD in a fast USB 3.0 non-UASP drive caddy is great!
Write-Protected drives - When booting from an E2B drive, the drive must not be write-protected. However, when connecting it to a Windows\Linux system to run software from the drive, it is useful to write-protect the USB drive to prevent infection from the user's OS. Write-Protected USB 3 drives are available from Kanguru or Netac.
2. Drive Size
Many BIOSes have a 137GB limit (bug) for USB drives (even recent BIOSes!) - any files placed beyond that point cannot be accessed on some systems (under grub4dos which uses the system BIOS). This means that the E2B partition must be the first partition on the USB drive and should not exceed 137GB to ensure it will boot on these buggy systems.
If your USB drive size is less than 137GB, then just use the big red button in the Make_E2B.exe GUI or run the \MAKE_E2B_USB_DRIVE (run as admin).cmd script. See here. If your drive is larger than 137GB, you will end up with a 137GB partition + a very small partition, so you should delete the 2nd small partition afterwards and then create a new 2nd Primary partition to store your own files.
If your USB drive is larger than 137GB (Flash drive or HDD), then you can instead use RMPrepUSB (or any utility) to create a 130GB NTFS partition (do NOT tick the boot as HDD C: option in RMPrepUSB) and then use another tool to create a second Primary partition. See here.
Unless you are an expert and have very specific requirements, I recommend you always use NTFS for your E2B USB drive and not FAT32 or exFAT.
You will still be able to UEFI-boot from .imgPTN files even if your USB drive is formatted as NTFS.
I do not recommend exFAT for E2B (though it should work OK for most purposes) because some Operating Systems cannot access exFAT partitions.
Also, SWITCH_E2B.exe is used with .imgPTN files and it is only fully compatible when used on NTFS E2B drives.
E2B can work on ext2/3/4 drives too, but it is not supported.
Windows Vista+ Install ISOs (MBR-booting + UEFI-booting) - Convert a working bootable USB drive or ISO to a .imgPTN file. Copy the .imgPTN file to any of the standard menu folders (e.g. \_ISO\MAINMENU or \_ISO\WIN) or to the correct \_ISO\WINDOWS\WINxxx folder)
Hiren's/DLC/DLCD/Strelec ISOs (MBR-booting) - Convert the ISO to a FAT32 .imgPTN file.
WinPE ISOs (MBR-booting) - Use file extension of .ISOPE01 or convert to .imgPTN file if that doesn't work