What is better: 2x8GB or 4x4GB DDR4 memory?

In a typical gaming PC with a motherboard that supports dual channel memory, the 4x4GB DDR4 memory module configuration has a slight advantage over the 2x8GB memory module configuration. This is given you are using RAM with the same timings and frequency.

However this is not the case in 100% of the games. There are titles that will see between 4% to 8% performance boost while others will see no boost at all. And usually the boost is more visible with games that are more CPU than GPU limited. In situations where you increase the resolutions and become more GPU limited than CPU limited the effect of 4x8GB is decreased.

It all depends on the application and a memory controller’s ability to maximize the memory rank. This determines how much of an impact it has on performance.

To maximize price/performance when you upgrade, we suggest using 2x8GB or 2x16GB DDR4 (for dual rank configuration) of memory. Four memory modules are really needed to maximize performance, but even then the difference is barely noticeable in real world gaming operation.

Why is 4x4GB faster than 2x8GB of memory?

A feature called rank interleaving is responsible for the speed increase. By using dual rank interleaving, the CPUs split commands between rank pairs to speed up memory access. To allow dual rank interleaving, your system needs four memory modules each of them being single rank. This is equivalent to slotting two dual rank memory modules. 

So, it’s about the ranks and not the number of modules.

Memory modules with higher capacity (16GB) usually have two ranks, while consumer grade memory usually has only one. The memory chips on a single rank module are all on one side of the PCB, while those on dual rank modules are on both sides.

However there are cases where some kits have chips on both sides of the PCB but are still single rank. You have to check your memory spec to tell for sure if the kit is dual or single rank memory.

Why 4x4GB memory does not not work as a quad channel?

It all depends on the platform. Any RAM stick will work as a dual or quad channel. The only thing  that matters is the platform. To be able to use quad channels you need a processor and motherboard that supports quad.

With Ryzen 3000 and 5000 series processors, for example, you have only dual channel support and no quad channel. 

It’s almost the same with Intel. Quad channel hasn’t been supported since 1151, so there’s no benefit from that. 

Quad channel, however, is available with XEON and Threadriper processors. 

Is there a difference between Intel and AMD when using 4x4GB or 2x8GB?

There is no difference in performance between Intel and AMD when using 4x4GB versus 2x8GB. If you gain performance in one game with 4x4GB on one platform, then expect the same with the other.