Registry Cleaners

I use ESET Smart Security, and I scan with CCleaner without issues

 

There are degrees of risk. A dedicated uninstaller such as Revo searches the registry only for entries specific to the program you're removing. Since the number of keys found are usually small it's also easier to confirm they relevant. Mistakes are still possible of course and regular imaging is a good idea in general, not just when you're going to work on the registry.

By the way, for managing startup entries I like Winpatrol. It makes it easy to get at the startups that run from the registry and there is an option to disable instead of remove them - safer.