Not for performance. (You might shave a microsecond somewhere, but you've already wasted a million times that by clicking the Clean button.)
However, if done properly, it can resolve discrepancies in the system that confuse the user or other applications.
To give you a hypothetical example (I can't remember if this is exactly the sort of thing that can happen, but it's similar to the discrepancies I've seen happening and fixed), imagine uninstalling Photoshop and still seeing .PSD file types showing up as "Photoshop Document" but without any valid icon. This would indicate there are stale entries in the registry, where e.g. the description is present, but the file type handler is absent, and would leave the user wondering why the word Photoshop is still present even though the application has been already removed.
Similar things can leave other applications confused too, e.g. the handler might be present but the program it refers to might have been uninstalled, and hence it might no longer be possible to open the file.
So yes, they might be "effective" in some cases, and a Properly Written cleaning tool Should Not cause problems. But in practice, I wouldn't highly recommend them unless you're willing to examine what the tool is actually doing. The potential to break something further is too much to risk for the possibility of removing a user-visible discrepancy unless the user knows and limits what the tool is doing.
1I wouldn't clean my registry if I'm just looking to speed up my computer. I would do that if I was experiencing problems related to the registry, or if a virus messed up something. If you are experiencing performance issues, I would check other things first. – MC10 – 2015-08-18T16:29:18.573
for the most part, cleaning your registery will do nothing to reduce the effort/time required for any particular atomic operation. There will be completely negligible effects from parsing a smaller file, or using slighly less ram to load them, but the registery is composed of tiny bits of information with a great deal of structure, so the size of the data is small both to load and parse, unless your system is so messed up that it won't boot anyway. – Frank Thomas – 2015-08-18T16:29:42.957
3The article you linked to is accurate. – fixer1234 – 2015-08-18T16:30:23.307
The links from the article are worth reading too – Tetsujin – 2015-08-18T17:31:38.793
2Be careful with these things; I ran one on Windows 8 and it didn't know about it, and it broke the Windows Store apps. So they can cause more harm than good (if they do any good at all). – Andy – 2015-08-18T17:40:43.740
Really? An answer from 6 years ago is still valid state of the art? Nothing changed? – Marina Dunst – 2015-08-19T17:10:54.460
Well I doubt the way the Windows registry works has changed much at all. Sure there may be different keys but the registry isn't and hasn't been a big factor on speed. – MC10 – 2015-08-20T01:45:53.210