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I am starting a WordPress multisite network with domain mapping and I am trying to think through my server set up. Right now, I only have one medium sized VPS but hopefully I will need to add more servers later so ideally the solution will also accommodate future growth.

My question is, would it be better to set up Nginx as a reverse proxy with Apache or use only Nginx? It seems like setting up Nginx as a reverse proxy would be easier and offer less of a possibility of problems but, on the other hand, would using only Nginx add substantial benefits?

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Unless you need Apache for some other specific reason, there's no real need to keep it in this scenario. It's only adding overhead, which you can ill-afford in a resource-constrained VPS.

nginx + php-fpm is a well supported configuration for WordPress; see their wiki for configuration examples.

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