I use an Epiphone Les Paul Custom (scale length 24.75") and have been running the standard 10-46's for a little while now. But even with a fresh set of strings, when tuned correctly open notes go sharp when played aggressively. I've been considering using a set of strings thicker all-around (11-49's) to try to counter this a little bit, but I don't really know if this would change anything. So my questions are, would using thicker strings counteract the sharp notes issue at all? If it does, would it be better to use an even thicker set? And would these strings have any noticeable effect on sustain? I know they will (probably) have a slightly altered tone to them and be "more difficult" to fret and bend, but what about the other variables?

I feel slightly guilty asking these questions, but when I search for the answers I get waaaaay too much noise.
It's possible that your guitar might not be set up properly, which could be contributing to those tuning issues, and if that's the case than it would need sorting. Similarly, if you were to switch to the heavier strings, you'd need to get it set up. I'm not really sure getting thicker strings would act as a counter to the sharpening of your tuning.
Or maybe it's just you fretting harder. Since you push the strings further, the note sharpens.
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Heavier strings have a tad more sustain, (more mass, more momentum), allow down tuning without floppy strings, but the down side is playability. You can't bend and well on the higher strings, and some people can strum as well.
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Is there such a thing as a heavy riff with out chugging on the e string?
i run 11-52' on all my guitars in standard tuning and i love them once you get used to them they feel easy to bend and then when you play lighter strings they feel crazy light. but i dont know if they would stop the notes going sharp... sorry
Well, it's not a tuning issue, it's just that for whatever reason if the string is played hard the note goes initially sharp, and then evens out. This can be more pronounced by down-tuning the bottom E to a D, and then playing it hard - it goes "whrrrrrrr!".

It's also not a fretting issue, as I'm referring to when they're played open.


USCENDONE BENE, while I haven't tried that before and it certainly sounds interesting, the problem isn't with tuning.
When getting aggressive you might have the tendency to fret harder making the notes sharp. I used to do it alot long ago but broke myself of the habit. Taller frets make its easier to do than short ones.
Yeah, thought it may be the jump at beginning of most chromatics. Sorry. I used to push up on my high 3 strings when I first started, but you said not fretting issue so idk. You can always alter the set-up a tad
your playing too hard... practise more and get your right hand movement as smooth as possible. its all about developing your touch - not too light, not too hard.
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No.... that is not the reason, if you're still confused, read my original post.