The most important of the three is the Museo del Prado, which houses the definitive Spanish art of the past 500 years - Goya, El Greco and Velázquez in particular.
But if you'd struggle to name three Spanish artists (getting stuck after Salvador Dali and Pablo Picasso) then the Reina Sofia might be more up your street, with excellent modern art from these two titans of contemporary art and many other examples of weird and wonderful art from the past 100 years.
If you are an art newbie and don't know what you want, many would still say you should see El Prado (it is that good, they say). However, I'd say that Museo Thyssen-Bornemisza might be a better compromise, as it covers art from medieval times up to the present day. If you find that you prefer older or newer art, you could always go to one of the other museums afterwards.
If you plan on visiting all three museums, you may be tempted by the Abono Paseo del Arte, a combined ticket which gets you access to each of these museums once. The ticket is no longer as good value as it used to be (many sites still claim it is 7.66€ - it has in fact gone up to 14.40€) but you'll still save a couple of euros if you know you will be visiting all three museums.
Entry into all of these activities is also free with the Madrid Card.
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