In theory, no, but if you're using an AMD Ryzen CPU, there's some nasty bugs related to VME instructions (which AMD appears to have no intention of fixing) that

In theory, no, but if you're using an AMD Ryzen CPU, there's some nasty bugs related to VME instructions (which AMD appears to have no intention of fixing) that break some DOS-based applications, including Windows 3, 9x, and probably the other DOS-based Windows versions as well but I never tried them. NT-based Windows works, though early versions do not perform as well as they do on Intel (my R7 1700 and 5700X run Windows 2000 VMs worse than my old i5-6600...I wish I was joking).