Why Mercantilism?

Mercantilism + statue of liberty + representation + caste system and cistine chapel would be nice if you have big empire.
 
Will it prevent the trade with our worst enemies penalty?

No, since the trade deals you make in the diplomacy are a completely different thing. The only way to prevent this is to terminate all deals including open borders.
 
I just wanted to add, Mercantilism is particularly useful on maps where you will not be meeting many other civs - archipelago for sure, and continents when you may be alone or only with one other civ to start (depending). You usually don't even meet the other civs until well into the game. By that time, you've had mercantilism running essentially without any penalty. In any case, it is most useful early in the game while foreign trade routes give you +2/+2 commerce instead of the domestic +1/+1, in other words, a small tradeoff.
 
Kamigawan has a good point: I generally play archipelago maps, and I usually discover astronomy a long time after the tech that enables mercantilism (what was it already?). Hence, mercantilism is an obvious choice. However, once I can trade abroad, I generally prefer foreign trade routes, because the yield is much higher.
 
One more factor to consider: your science/culture slider settings. Or asked other way around: how many % of your commerce goes towards gold? If the % is low (or none), merchantilism can really boost your income (by setting up merchants). That is because trade routes count towards your total commerce, not gold created. Logical...if little (or none) of your commerce is turned into gold, you won't get much gold :) So, if you are short on cash but wish to keep science high (don't forget to use representation too), merc is a good choice for some time.

Also, it somewhat depends on the difficulty level I think. In higher settings, I assume the AI will develop their cities much quicker, so trade routes to those cities will be more profitable. On lower settings, your own cities will always be bigger than the AI's, so trade routes aren't that great until the late game. In this case merc is much better to keep around for a longer time.
 
If we go with the assumption that you are running representation, and your science slider is 50% (50% gold, no culture), then that means every merchant specialist is worth 6 coins of commerce. Magnify that by the increased great merchants you'll be generating and that's a fair amount of cash. That's actually not too bad if you don't have many sea trading (harbors) going on.

I think the main problem is not mercantilism itself, but it in comparison to free trade. Free trade has a lower upgrade cost AND gives you a +1 trade route. That's results in a butt load of money and science which is hard to beat.
 
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