Here's my take on cleaning or 'tuning up' the registry with any 3rd party software:
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First off, one big thing about registry cleaning is it is by no means and should not be a computer maintenance task. Clearing your browser's cache and cookies every week? Great, no harm there. Running your favorite registry cleaner every week?
NOT GREAT.
If we're being honest and straightforward here, cleaning the registry is an entirely unnecessary thing to do. So far, what I've said makes it sound like I despise registry cleaners. Do I? No, I don't despise them, but as I said, they are unnecessary and if used carelessly can render your Operating System a paperweight.
So why would you even use a registry cleaner in the first place? Well, they have to do something right or they wouldn't even be allowed to be sold (if paid for) or if they were free (CCleaner for example) there would be a huge backlash, more than what there already is in IT with regards to opinions based on registry cleaners.
Registry cleaning software is useful mainly for one thing, and it can be done very well depending on the algorithm the cleaner software itself is using, and that's removing remnants of old uninstalled software or entries with now invalid path names. At times, it can also possibly be useful for removing traces of malware that may have been stored in the registry that was not successfully removed after running a virus scan, etc.
Other than that, it's not going to do anything. It will not increase your system's performance by any means whatsoever. Nothing noticeable. A 'smaller registry' in theory would have one assume that things load faster, etc, but in reality there is no performance difference whatsoever.
For reference, take a look at this:
Mark Russinovich (Author of the "Bible",
Windows Internals, co-founder of Winternals and Sysinternals, and since both companies were bought by Microsoft, now a senior Microsoft employee) was asked: