Summary
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Lower rates for a lifetime campaign; focus on personal conflicts to save the world.
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Add opponents to challenge your players; create competition and ambition for the role-playing game.
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Include new rules such as school grades or customer service for non-combat tasks.
Dungeons & Dragons are traditionally fantasy adventures with fire-breathing dragons or undead wizards wreaking havoc while a group uses their power to save the world. Using only the D&D rule system and a few settings, you can create a variety of campaigns in unusual settings suitable for casual players or veterans looking for something new.
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Slice-of-life campaigns embody the heroic fantasy of D&D and make conflicts more personal and social, enhancing the role-playing aspects of the game while reducing the need to swing swords. While this is the correct way to play D&D, there are more than a few tweaks and considerations needed to get the most out of this style of campaign.
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Drop bids
The main aspect of the time-of-life campaign is the simplistic story, with far less lethal stakes than a typical fantasy game. Instead of mining powerful relics to prevent the lich from covering the world in darkness, your players can instead figure out how to stop the carnival.
This also means that there shouldn't be any character deaths, and knowing that, your players will create their backstories and characters in a way that they know won't get burned halfway through. There should still be the possibility of failure, but life should not be at risk, only livelihoods.
Failing a slice of life can be scarier than traditional high fantasy, while trying to make up with a friend can be harder than killing a gelatin cube.
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Add opponents
The role-playing aspect is central to Time of Life, and the best way to challenge your players is to give them opponents who are always fighting each other. This may simply be a reflection of a party with more caustic views and stronger ambitions.
This opponent could also just be a single person who would otherwise have to be quite powerful to actually challenge more than four players. While they may not be the main antagonist of the campaign, they should give your players something to overcome or stand against.
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Adapt pre-written campaigns
Changing something familiar to a new format can make it easier for players to get into character and better understand the stakes and villains. This could be using the Curse of Strahd setting and turning Strahd into a brutal boss and your players into disgruntled employees.

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Ghosts of Saltmarsh includes ship and crew rules that make for a great seafaring campaign where your players travel to unique locations in search of crew members and stories to tell. Strixhaven: A Curriculum of Chaos is already a slice-of-life campaign setting perfect for magical school themes.
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Include new rules
At lower stakes, there's less of a focus on combat, and it can feel like you're taking away some of the mechanics of the game, forcing players to rely on role-playing to run the campaign. By including unique rules for customization, you can add challenges that will force your players to take risks.
In a school campaign, this can have players scrambling to determine the results of their schoolwork and adjust bonuses based on their performance. If you're running a business, you can add rules to keep or lose customers and which magical items in stock are causing havoc this week.
Strixhaven has rules for jobs, extracurriculars, exams, and even relationships that can be used in any setting.
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Give your NPCs more depth
More so than your average fantasy game, in a lifetime campaign your players will interact with NPCs much more often and almost under a microscope. You'll want to make sure you understand their motivations, and even give important NPCs their own backstory.
This is especially important for rival characters and antagonists, as players will be looking for anything they can to predict their next moves. It also gives you room for backstabbing and dramatic turns that would otherwise have to be perfectly executed in a normal D&D campaign.
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Reduce combat
Although D&D rules focus heavily on combat rules and options, your players won't have six to eight encounters a day and will often go an entire session without swinging a sword. This is not a bug, but a feature of lifetime campaigns that allows your players to focus on other mechanics or RPGs.

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It will also provide a fresh look at spells that are often overlooked as the use cases for Druidcraft and Grease become much less niche. Consider giving spell scrolls and magic items that enhance non-combat abilities or add unique curses that affect behavior and roleplay instead of adding elemental damage types.
Allow players to use combat abilities in creative ways, such as making an attack roll to open a door or chest.
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Start low
Players with access to 5th and 6th level spells can quickly overcome a life shard campaign, making the average adventurer or NPC weak against their overwhelming abilities. Players should start at level one and leveling up should take almost twice as long as normal, ensuring that your players can still fight without dragons and buffs.
You'll also want to make sure you don't adventure until level 20, or even level ten, because then the campaign loses its ability to support the slice-of-life theme. However, if everyone agrees to allow the company to move, it could lead to an interesting, high-stakes conclusion to what started at wizarding school.
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Turn on the mysteries
Since in slice-of-life campaigns, your players rarely get to show off their abilities and spells, giving them a puzzle to solve allows you to show off what their characters are capable of. These are usually low-stakes adventures that lead to important clues that can reveal deep truths about familiar NPCs or places.
This kind of information should be powerful, allowing your players to use it as leverage as well as target them.