Spanish 21 differs from traditional blackjack primarily in its use of a Spanish deck, which has no eights, resulting in 48 cards instead of 52. This variation also features unique rule modifications that offer more favorable conditions for players, such as the ability to double down at any time, surrendering after doubling, and bonus payouts for specific hands. These changes not only alter the strategy involved but also create different gameplay dynamics, making Spanish 21 a distinct and often more player-friendly alternative to standard blackjack.