Incompatible Add-Ons

• The 64-bit version of Internet Explorer can only use 64-bit add-ons, so the number of add-ons compatible with 64-bit IE is very small compared to the regular version of IE. For this reason, you may want to hold off making it your main browser.
  
  

Memory Protection for Safety

• IE 64-bit has features that prevent some of the more common memory-related browser hacks. This protection is also available on 32-bit versions of Windows and Internet Explorer, but is built into 64-bit IE.
  
  

Usability

• Some sites do not support 64-bit Internet Explorer. Microsoft also warns against making it your default browser in case you "forget" it's the 64-bit version and can't access a website. You can add a button to 64-bit IE that allows you to click it to open a website in 32-bit Internet Explorer (see Resources).