I boot in Native 16-bit mode on my Intel I5 based computer on the SATA 512GByte drive, no problem running 16-bit code and PharLap DOS extenders. The latter can use up to 4GBytes of memory, and can use the VMMDRV that was offered under PharLap.
I use the FDISK that comes with FreeDOS to partition the drive as a single FAT-32 partition, and use FORMAT/s that comes with Win98 to make the C: drive bootable. I make the drive dual-boot DOS7.1 (win98) and XP. I'm using Panasonic CF-53 and CF-52 laptops, which offer native USB support for devices under the BIOS, which includes DOS. I use these to develop embedded code running on an ICOP VortexDX and now an ICOP VortexDX3. I also picked up an ICOP VortexMX that was a "thin stack" network node, but makes a great embedded processor. The ICOP Vortex line runs the PharLap extenders without problems. PharLap runs in 32-bit mode under DOS, gives access to PCI functions.
The CF-53 is "very compatible" with older software- the RS232 is capable of running the JDM device burners, I ended up writing my own driver for the JDM programmer for an Ampro PC104 computer, works with the CF-53.
The Panasonic Toughbooks use drive caddies, I just pop the caddy and put in a WIN10 disk/caddy when wanting to use it in 64-bit mode.