Synergys

[Flavour similar to vanilla]

Whats The Best Synergy Youve Ever Got? Personnaly mines Brimstone+Lawst Contact
Also Plebs Dont Just Say Epic Fetus Plus Every Bomb Item

[.Keks]

Mom's Knife + Pause
Haven't been more OP in almost 600 h of Isaac.

[roboticman1236]

its probably a old one but fun nonetheless isaacs heart and blood rights

[Neuromonada]

Gnawed Leaf+Halo of Flies.

[SCARY and EVIL]

Brimstone/Mom's Knife + a keyboard + a monitor

Seriously Edmund please nerf the ♥♥♥♥ out of them

[Mori]

Mom's Box (with Curved Horn and gulped Cancer) + Death's Touch + Mom's Eye + Sacred Heart + Sinus Infection + Guppy transform.

[fvkjenny]

epuc fetis + erry bom itum

[beautheschmo]

In terms of just straight up 2 item synergies, my 2 favorite are probably:

Ludovico Technique + Cricket's Body (I got this on a run with a minimum-damage Eden and an experimental treatment that dropped damage and it still deleted everything)

Tech X + Eve's Mascara (Mascara doubles the damage, and then heavily cuts the speed, drastically increasing the amount of damage a single shot will deal. The downside is, of course, that it takes significantly longer to charge, but a single shot will usually clear most, if not all, of a room and can be charged before walking through the door).

[ɹǝǝpᴉnbS™]

Assuming we can count item combinations from the original as well (They play out more-or-less the same across both games), My best run has been a combo similar to the set-up you get on Slow Roll: Chocolate Milk + Cupid's Arrow + Polyphemus + Mutant Spider

Chocolate Milk was picked up from the first Treasure Room, I nearly decided to skip it but I'm so glad I picked it up. The second treasure room yielded Cupid's Arrow, The third yielded Polyphemus, The fourth awarded the Mutant Spider. Damage Up pills were also fairly plentiful across all floors.

From the third floor onwards I was able to kill practically everything the moment I enterred the room, I missed Basement Baby but was able to pick up every other no damage achievement on this one run alone. Eventually picking up Rebirth after the original, I was so glad to see a variation of this ridiculous combo implemented.


Nothing ever has compared to item set-up, And I doubt it ever will. One can dream though.

[txh0881]

The Forgotten with IPECAC and Chocolate Milk.

IPECAC makes his melee attack be a melee bomb that does not hurt you. With Chocolate Milk, the charge makes your melee massive, giving you huge damage with huge range. Together, it allows you to one-shot weaker bosses. Several "One Makes You Larger" Pills make your attack even larger, allowing you to clear normal rooms moments after walking in.

I beat Mega Satan and Delirium in the same run with minimal effort without needing to use the body as a meat shield.

[CyborgCthulhu]

I just had this insane run, 2 steam sales + restock + chaos = utter madness

[John Orbit]

Sacred Heart + Crown of Light + Godhead + Cricket's Head + 3 Guppy Items + Spun!...
Gotta love Chaos and Steam Sale in Greed Mode!

[John Orbit]

Really, just Chaos in Greed mode.
That's all you need.
It's guaranteed Guppy unless you get it on the last two floors.