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So I've been reading through some guides in preparation for a Clean Hands playthrough - killing absolutely no one, using the Non-Lethal option for all the assassination targets.

However there's one point that seems a bit muddled. The guides say that if going for the Clean Hands achievement, it might be a good idea to avoid Granny Rags altogether, as interacting with her leads to that bit in the Flooded district and it's very hard to get out of that without killing someone.

However, they warn, avoiding her altogether makes it impossible to get the Gentleman Callers and Street Conspiracy achievements.

Gentleman Callers is obvious, but Street Conspiracy includes the non-lethal option for the Pendletons.

So basically what I'm asking is, can you still use Slackjaw to take out the Pendletons without killing them if you avoid Granny Rags?

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You don't need to kill the Gentleman Callers, just use sleep darts on them. That way you won't kill anyone and still get Granny Rags rewards.

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Yes.

Unless you kill Bottle Street Gang members and make them your enemy, nothing should prevent you from taking Slackjaw's quest to neutralize the Pendletons.

It's not necessary to completely avoid Granny Rags to get the Clean Hands achievement, as none of her quests involve killing anyone. In her first quest, rendering the gang members knocking on her door unconscious will be counted as succeeding, and she will give you a rune as a reward. But note that poisoning the distillery for Granny Rags is increasing current chaos.

You can do unlock both Gentleman Caller and Street Conspiracy achievements in the same playthrough by doing both the side-quests for both Granny Rags and Slackjaw. And when you meet them in the sewer, you can just save before you take side, complete their last request, and the achievement should appear. Now you can just load your save and take the opposite side and get the achievement there too.

Note that it's possible play through the entire game without killing anyone and without being seen, and still get every rune, bone charm and painting.

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