Does storyline progression lock off starting any side quests?

[Insane Scientist]

I finished a playthrough of the game's story and with certain story events that happened it made me wonder if main story progression can prevent you from starting certain side quests? Basically, if I wanted to do every single side quest in a single playthrough could you do that if you waited until beating the main story to start side quests?

[z00t]

Short answer, yes.
Certain side quests are unavailable when the NPC's who give them are somewhere else for that part of the story.
Some of these missions can show up as 'Blocked' in your mission log if you have them already. All this means is that if you do compleet them, you will not be able to hand them in. It does not mean that you cannot do them.
If you waited until you defeat the Warrior, all missions will be available.

[Zen_Disaster]

First, you don't want to beat the main story before starting side quests ~ many of them drop the game's best loot which can really help you doing the main story. As well, story~wise many of the more important sides "fit" better if done as encountered. That said, it's fairly easy to overlook or miss some sides in NVHM, less so in TVHM and almost impossible in UVHM. At least that's the way it was for me. But "lock off" as such, yes I believe there were a couple like that but honestly I don't remember which ones as it's been years since I was playing BL2 aggressively. Yes, you can complete all the missions in the game in a single playthrough ~ I'd always chose UVHM as that playthrough.

[Insane Scientist]

Thanks for the tips