1999 Mode will essentially add more difficulty to the first-person adventure by forcing players to closely examine their decisions throughout the campaign.
Players will need to plan ahead when consuming resources and take more accurate shots during combat, while damage has more impact on health.
Choices made in specialisation will also be important, where weapons outside of chosen fields will be useless.
Developer Irrational Games introduced the mode following a survey that suggested players wanted an extra challenge.
"We want to give our oldest and most committed fans an option to go back to our roots," said creative director Ken Levine.
"In 1999 Mode, gamers face more of the permanent consequences of their gameplay decisions. In BioShock Infinite, gamers will have to sweat out the results of their actions. In addition, 1999 Mode will demand that players pick specialisations, and focus on them."
BioShock Infinite will be available on Xbox 360, PlayStation 3 and PC later this year.
> Read our preview of BioShock Infinite
> Read our BioShock Infinite interview with Ken Levine
Watch the latest trailer for BioShock Infinite below: