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In my mind the best registry cleaner is one which reliably fixes problem entries but doesn't itself cause problems in the process. The products most likely to possess these qualities are those that are conservative in operation and confine their cleaning to removing definite and unambiguous errors. I say this because I have seen as many problems created by registry cleaners as problems solved. This view flies in the face of many who consider, for whatever reason, that the best registry cleaner is the one that finds the most problems. To me such products are dangerous and not worth owning.
That said, my top recommendation is Toni Helenius' free EasyCleaner . It's a good reliable, conservative performer that will fix all major problems with a low risk of creating problems of its own As a bonus, it will also detect duplicate files and help you clean up temp files to make more disk space. One of its best features is a regularly updated "blacklist" of registry values that should not be cleaned. I'm sure this contributes to the products excellent record of causing few problems. Remember though, as with every Registry cleaner, to back up your Windows Registry before use.
A reasonable alternative is using Free Registry Cleaner . I've only had a couple of reports of it causing problems but it has an easy to use backup and recovery feature that will help you out should you get into trouble.
Many folks like RegSeeker which combines registry cleaning with some registry management features. It's a nice product but its cleaning function is too aggressive and problem prone to allow general recommendation.
CCleaner , the class-leading disk cleaner has an inbuilt registry cleaner as well. However I'd never leave anything as critical as registry cleaning to a general purpose product; for this you really need a specialist utility.