Get it wrong and your system could become unstable at worst, removing the wrong (but crucial) item could crash the system entirely. The dangers of messing with the registry are not to be underestimated. If you're going to do it anyway, go to the Microsoft site and download the Live OneCare Safety Scanner, and let that examine your registry for problems : it's a Microsoft tool, it will be configured for your OS, and it will be more trustworthy than most 3rd-party offerings. Basically, any performance improvement from stripping out registry items is going to be small, and the risks from using an over-enthusiastic registry cleaning tool are potentially considerable. In this I am following Microsoft's advice, as given in a couple of their KnowledgeBase articles.
If you don't need to clear anything from the registry, my advice is to leave it alone. One feature of it that I don't like is that Quick Clean tells you nothing before, during or afterwards about what gets deleted - just the total number of files - so if it changes anything in the registry you won't know what it's done.
In the settings on mine for Quick Clean I don't see the option for Registry Clean, but it does it anyway so maybe it's one of those things that you can't undo once it's set (which I would say is a definite bug in the program, but never mind).
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