There are two 64-bit Windows platforms: x64-based and Itanium-based.

The x64 processors are compatible with the x86 processors at a hardware level and x86 instructions are executed natively by the micro-architecture. Therefore, execution speed under WOW64 on x64 is similar to its speed under 32-bit Windows. On the Intel Itanium processor, more software is involved in the emulation, and performance suffers as a result.

On the Intel Itanium processor, WOW64 adds significant overhead if two or more instances of the same 32-bit application are running concurrently. This is due to the native 8 KB pages on the Intel Itanium, which complicates the emulation of the native 4 KB pages on the x86 architecture (more pages are marked as writable; all writable pages are private to the process). This is not the case for the x64 processor.

As far as Remote Desktop Services (RDS) is concerned, only the x64 platform is supported. So the question really boils down to: “How does moving from x86 to x64 RDS platform affect me?”

Some of the most common FUD around this is regarding application compatibility.

In this post, we will look at a high-level overview of 32-bit application support in Windows Server 2008 R2 and point you to various resources that should help answer most of your questions related to the same. Please note that 16-bit DOS, Windows, or OS/2 applications are not supported on 64-bit Windows.

Source: http://blogs.msdn.com/rds/archive/2009/09/02/what-does-64-bit-only-change-about-windows-2008-r2-rds.aspx