Many BIOSes (even modern ones) have a bug in their USB driver code when means that they cannot access sectors on a USB drive which are beyond 137GB.
As this bug is in the USBcode, it does not affect UEFI-booting or booting from an internal SATA/IDE/SCSI hard disk.
If you are booting from a USB drive which has a first partition of a greater size than 137GB, then you may find that some payload files (or even E2B) will refuse to run.
grub4dos (used by E2B) uses the BIOS for file access on the USB drive.
Typically, you will see an E2B message like 'ERROR: xxxxx.iso is not contiguous (or is corrupt or missing)!'
If you press a key, you may then see a grub4dos 'Error 16: Inconsistent filesystem structure' message.
This indicates that some part of the file could not be read (or was corrupt).
If you are using a large USB drive for E2B, you should create a first partition of less than 137GB and place all E2B and payload files in the first partition.
Once you have booted to grub2, linux or Windows, the 137GB limitation will disappear because those OS's do not use the BIOS for disk access.
WARNING: THIS BIOS MAY HAVE PROBLEMS ACCESSING SOME FILES ON THIS DRIVE! - E2B will usually give you this 'BAD BIOS' warning when it boots from such a buggy BIOS if your USB drive is greater than 137GB in size, because it tests to make sure it can access sectors at the end of the last partition. If you see this message as E2B boots, you can expect any file located on the USB drive which is beyond 137GB to not be accessible or not load properly!
You can try to reduce the E2B partition by removing a few large payload files and defragging the USB drive using a Windows defrag tool. Then use the Windows Disk Manager or AOMEI Home Partition Master to reduce the size of the first partition to 137GB or less. If the USB drive contains a second small partition, you can delete it and then create a new Primary second partition which you can use to store files on (for instance backup images, etc.). This will work because once you have booted to Windows or linux, there will be no problem in accessing the second partition which is beyond 137GB on the USB drive.
Note however than Windows will only see the first partition on Removable types of USB drive.