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For someone of average strength and stamina? No, it's just fine, though heavier than the Kindle. I never had any problems with it while I was still stealing (er, borrowing) the s.other's nook. For someone with bad arthritis or particular muscle weakness I suppose it could be a little too heavy. I'd say it's a little heavier than a normal mass market paperback, but noticeably lighter than a hardcover.
Edit: I was assuming you were talking about the classic nook. The nook color is definitely heavier, but I've not spent much time with one.
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