What is the best caching option for WordPress multi-site on non-shared hosting?

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Basic answer to “what plugin” would probably be W3 Total Cache. It is one of the most functional and actively developed plugins at moment. However complete performance chain is much longer that WordPress plugin alone can handle.

  1. Web server (Apache or something else) configuration (response time, time to first byte, headers).
  2. Database (time spent processing queries).
  3. PHP/WordPress (page generation time, memory consumption).
  4. Front-end performance (amount of HTTP requests, bandwidth).

Good start would be static caching plugin (like W3) with opcode memory-based cache like APC.

But from there there are way more (and way more complex) things you could do, like content distribution networks, alternate web servers, etc.

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