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Yes it can, in fact it almost feels like it was meant to be done after the main story. I beat it yesterday and won't say why.
Post edited June 05, 2016 by flclafi
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Lannister: so.... with blood and wine out now, can anyone answer my question ?
Yes it can. In fact it is *much* better (for one particular reason) if it is played after the main quest.
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Lannister: so.... with blood and wine out now, can anyone answer my question ? all the answers i found on the I-net are pretty vague...

Cheers and Thanks,
L.
Finished it now, have already finished the main quest and the first DLC some time ago,

some quests and conversations "SEEMS" only happen, when you have finished the game ...