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I may have written an entire guide on how to think about an A20 run.
https://steamcommunity.com/sharedfiles/filedetails/?id=1613845715
And wrote a thread about just general tips that are good at any ascension:
https://steamcommunity.com/app/646570/discussions/0/1779387743942133058/
Don't take cards unless they work with what you've already got, or add something you need.
The number of times I've taken catalyst before I actually have a source of poison... A smaller deck now is much more important than the hypothetical perfect deck you could build if the right cards come up later.
The other one is:
Don't over-value combo cards and don't neglect defensive cards.
Power Through might be dull compared to the combo possibilities of Dual Wield, but if you've got damage coming in and need to use three Defends to stop it then Dual Wield is dead weight. If you grow your deck without adding a few defensive cards then later floors will overwhelm you.
It's true that certain combo cards that are exceptionally powerful, are dangerous to take early on without the rest of the combo - things like Corruption without a proper backing.
But generally, you need to take the risk if you're presented with it. If on the first fight, I get Barricade as one of my picks, I'll take it, even though it's almost 100% useless until later on.
On higher ascension levels, you're better off taking the risks and just ending your run early, instead of wasting the time trying to be more precise and ending up on act 3 without the necessary cards or relics to win.
If I were to give two pieces of advice: 1) Take those risks, and 2) Don't undervalue removing cards. You should ALWAYS try to remove cards whenever possible.
And that's part of why you're only playing at A16.
Edit: while I'm at it I want to touch on a different issue: Strike vs Defend. People say "Strike is worse than Defend, so I always remove Strikes", which is oversimplified. I agree that Strike is worse, but it doesn't mean that it's always correct to remove a Strike while leaving Defend. Think of all the turns when you have enough block that Defend does nothing. There's no such thing with Strike, you can always use more damage.
1: Unless you get some insane card draw and/or have a niche deck (a curse deck for instance), deck size should be roughly 25 - 30 cards. An exception can be made for ironclad if you have lots of exhaust and/or corruption.
2: Try and get an AOE early. An early whirlwind as ironclad is very powerful. Silent you have either shivs (sort of Aoe as its free damage) or something like noxious fumes. And defect has beams, but failing that you can just rely on orbs in a pinch.
3: Avoid elites in Act 2 unless you have a very good deck with lots of clear (buffed up whirlwind, corpse explosion, lightning storm) and a solution for the stabbing book (vulnerable/bludgeon, catalyst, thunder strike).
4: If at >50% health you should think about resting, especially later on (post act 1). You can aim for a late Apotheosis in the shop
5: You should always take one of the red options on the neow pick. Dont be afraid of relics like runic dome or even things like ectoplasm/coffee dripper. Extra energy is always good. Just hope you dont roll white elephant.
6: Take ? rooms whenever possible
7: Early card picks should be: Damage > Defence > Powers
8: Avoid going for really specific niche type decks. They are great when they work, but very difficult to set up and more often than not will just get you killed.