Hand Size refers to the number of cards that can normally be drawn into your hand at the beginning of a Round or after playing a Hand or Discard. It also determines the number of cards that are drawn when opening an Arcana or Spectral Pack. The default hand size is 8.
If the number of cards in hand meets or exceeds your Hand Size, you will not draw any cards after playing a Hand or Discard unless and until the number of cards in hand is fewer than your Hand Size. Whenever the number of cards held in hand falls below Hand Size after playing a Hand or Discard, cards will be drawn into your hand from your Deck until the number of cards in hand matches your Hand Size. The only exceptions are when the number of cards remaining in your Deck is insufficient, in which case you will simply draw all the remaining cards in your Deck, or when facing The Serpent Boss Blind, where exactly 3 cards are drawn after every played Hand or Discard, ignoring Hand Size.
A smaller Hand Size can be beneficial with e.g. 
Blackboard, since its effect is triggered when there are no (non-wild) Diamonds, Hearts, or Stone Cards left in hand after playing a Hand, which is easier to achieve with a smaller Hand Size.
However, in all other situations, a larger Hand Size is more beneficial since it allows more options and flexibility when playing hands or discarding and allows for the possibility of triggering more card held in hand abilities. Furthermore, it allows more options when opening Spectral and Arcana Packs by providing more card options to apply the effects to, and in the case of 
Sigil and 
Ouija, where the effects apply to every card in hand, having a larger Hand Size increase the impact of those cards.
Hand size can be increased or decreased by Vouchers, Jokers, Spectral Cards, or Boss Blinds.
Increasing hand size[]
Painted Deck starts with +2 Hand Size, increasing the starting Hand Size to 10.
The 
Paint Brush and 
Palette Vouchers each add +1 Hand Size.
Some Jokers increase hand size:
Turtle Bean adds +5 Hand Size (reduces by 1 each round)- Troubadour adds +2 Hand Size
- Juggler adds +1 Hand Size
Decreasing hand size[]
Some Jokers decrease the player's hand size:
- Merry Andy reduces Hand Size by -1
- Stuntman reduces Hand Size by -2
The Spectral Cards 
Ectoplasm[1] and Ouija reduce Hand Size by -1.
The Boss Blind 
The Manacle temporarily reduces Hand Size by -1.
Forced cards[]
It is possible to hold more cards than your Hand Size in certain situations. This can happen when cards are added to your hand outside of normal drawing.
This can be done using 
Familiar, 
Grim, 
Incantation, or 
Cryptid. Some Jokers also force cards into your hand: 
DNA[2] or 
Certificate. The boss blind 
The Serpent can also let you hold more/less cards than your hand size.
- ā Each time that Ectoplasm has been used in a run increases the Hand Size by penalty by another -1 for subsequent uses of the card, e.g. using Ectoplasm 3 times in the same run decreases hand size by a total of 6 (1+2+3)
- ā DNA operates by copying a played card and adding it to hand. The played card removes a card from hand which is then replaced by the copied card, resulting in no change to the number of held cards (although it allows for the sum of played cards and cards held in hand to exceed Hand Size, which is not normally possible). However, DNA is compatible with Blueprint and Brainstorm, and when its effect is copied in this way, multiple copies of the card will be added to hand, therefore enabling DNA to be used to exceed the normal Hand Size.