Quote:
Resistance reduces the damage you take when you're hit. Defense reduces the chance that you'll be hit in the first place.
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Originally Posted by DimMak
What's the Difference between Resistance and Defense?
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Yeah. Defense means avoiding damage. Resistance means reducing damage.
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www.paragonwiki.org/wiki/Defense
www.paragonwiki.org/wiki/Resistance
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In short, 1% Defense is about 2% Resistance. (25% Def = 50% Res) You cannot have 100% Resistance, or a 0% chance to be hit. You'll always have a 5% chance to be hit, and take some damage when you're hit.
Defense keeps you from being hit for long streaks of time, but does nothing to reduce the damage when you are hit, so it's random. You could go for a long time without taking any damage at all, and then suddenly drop when you got unlucky. Resistance is more steady, but you're sure to lose HP, so eventually you will run out and have to either retreat or just let yourself die... I mean, be defeated. 
Hmm. Original question has been answered. Should I blather on? Yeah.... I think I should. Oversimplifications follow.
Defense works better at the top end, for almost everyone, than Resistance. There's a lot of Defense available through a lot of sources, making it easier to GET to the top end.
However, once Defense is "capped" more does nothing. The same is true for Resistance, but there are fewer ways to increase your Resistance, and the ones that exist tend to increase your Resistance less, so it's less likely to come up.
From which one may conclude that Resistance is "more likely to be useful" than Defense. Depends how likely you are to be buffed, I guess.
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What's the Difference between Resistance and Defense? If I get hit with Headsplitter, what does it do to my HP with say 50% defense and then say again with 50% resistance?
Sorry if this has been asked before, a link to that thread works too if it has.