Microsoft recommends using System.Runtime.Caching for all caching purposes. See this: http://msdn.microsoft.com/en-us/library/dd997357.aspx
Although, I have come across a couple threads where people are having issues with the MemoryCache.Default instance. After a while, it stops working properly. Any item you add using the Add or Set method does not actually get added to the cache. I tried the same and was able to reproduce this issue with explicitly calling MemoryCache.Default.Dispose() method.
Here are the links:
MemoryCache Empty : Returns null after being set
http://forums.asp.net/t/1736572.aspx/1
My recommendation is to use the System.Web.Caching (HttpContext.Current.Cache)
UPDATE:
This issue has been fixed by MS. Check the accepted answer in the post below:
Runtime Cache Issue Resolved