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It has been always said that when you clean the folder %windir%Prefetch you give your system and applications more performance.
Actually, thats one of the fables around Windows. Each time you start your computer and each time you open a program that you commonly use, Windows keeps track of information required to start the computer or that application and saves theses information in small files (called Prefetch entries) in the Prefetch folder to use it later to help speed up the computer start process or the application start time.
Thus, cleaning the Prefetch folder doesnt improve performance at all. Instead, it slows it down. It makes Windows uses longer time to start, and makes your favorite programs take longer time opening. An analysis did by TuneUp Systems results in a noticeable slowdown during Windows boot-up time and all applications that are commonly used took significantly longer to start after cleaning Prefetch.
Obviously, you do not need to deal with Prefetch entries manually, Windows handles them all. Actually, Windows Vista (and future systems that support UAC) helps protecting the Prefetch folder by using UAC (User Access Control, read more here) to prevent unauthorized access to this folder.