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As you reach the end, you get 3 missions, each indicating that one of the 3 main factions (the NCR, Caesar's Legion and Mr. House) are watching you and if you continue to help the other 2 factions you'll be treated as an enemy and fail any remaining missions with those factions.

I am wondering, what is the last mission I can do for each of the main factions before they hate me? This would be under the assumption that I've done NCR and Legion side quests before triggering the Reputation Reset with them after I made contact with Mr. House.

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marked as duplicate by Billy Mailman, Gigazelle, Schism, Meraj99, 3ventic Jan 5 at 11:01

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The NCR and Caesar will warn you with the Don't Tread on the Bear and Beware the Wrath of Caesar quests respectively. When you see one of these quests appear, you're about to piss off a faction. Completing another quest from the faction you're working for will permanently end their mission chain. Dropping your reputation with the NCR or Caesar will also cause this.

Mr. House does not have a trigger that stops you working for him but the other three all involve killing him at some point. Unsurprisingly, this stops you working for him.

Yes Man will never lock you out of his mission chain regardless of who you work for or even if you kill him (he just uploads his personality into another securitron). If you plan to complete the game with him you can work for other factions right up until the final battle.

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