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Well, it's not "safe", but I imagine you could get away with it in a situation where you knew that only one computer's copy of Calibre was active at any given time. Like for example if the library in question is your personal library, not shared with anyone else in the household, and you'd like to access it sometimes from your laptop and sometimes from your desktop but never from both at the same time. Just make very sure that you don't break that rule. If both copies of Calibre are active at once they could both try updating the library's database simultaneously and badness will ensue.
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