Let's try to lay this 1 year old thread to rest again. @
DasDonster, in your situation it sounds like you want to use the USB flash drive for non-bootable storage. You want to copy the ISO files themselves to the flash drive, then mount the stored ISO files to do an upgrade with. If you want to use the USB flash drive for storage only, then you want NTFS. It allows you to format a flash drive over 32 GB. It allows you to have individual file sizes over 4 GB. It allows you to have an insane number of files/folders. It allows you to keep all the file security settings. It is now a mostly universal file system that is compatible with almost every modern operating system.
If you want the USB flash drive to be bootable then you want it to be FAT32. When you purchase a Windows 10 installation flash drive from Microsoft, it is FAT32. If you allow the Media Creation Tool to create a Windows 10 flash drive for you, it is FAT32. If you allow Macrium Reflect to create a rescue drive, it is FAT32. The reason is that FAT32 is the standard file system that all PC BIOS/UEFI firmwares are required to boot from. All Windows 7/8/8.1/10 installation ISO files are designed to be extracted to FAT32. Modern system imaging programs such as Macrium Reflect will spit up the image it creates into chunks that will fit in the FAT32 file size limits.
The limits of FAT32 are 32GB total for the USB flash drive and 4GB individual file size. There is some smaller limit on the number of individual files and folders but you probably won't hit it, especially if you are using the flash drive for booting purposes.
Also, @
Dandonster, I highly recommend that you have at least 1 bootable USB flash drive created for system repair/recovery purposes. You want that one to be FAT32, you want the FAT32 partition on it to be marked as Active, and you want to extract the files inside the ISO file to it rather than copying the ISO file itself to the flash drive.