Happy to help. What comes in my mind is that the driver of the audio card is taken first by some other program that keeps it and Reaper cannot see it to initialize it. Maybe you have an internet browser open, or an aplication that uses audio such as messengers or players of some kind. Or a multimedia application that locks the driver. Try to go to the windows Control Panel, on "Sound,Speech and Audio Devices". Then "Audio Devices" On the tab Sounds, put "No Sounds", On the tab "Audio" choose another card, not the one you use for Pro Audio, Do the same on the tab "Voice", On the "Hardware" tab, go to the list and choose your Presonus, press "Properties" and on the new window that opens press the tab "Properties" again, then choose your audio card once again (Presonus), expand the tree and choose the card and press the button "Properties" (Yeah, I know, kind of retarded use of various properties windows, hehehe), and on the new dialog box choose "Do not map through this device", that way, the operating system will not use the Pro card in order to play multimedia content that is low res, or will lock your card. Try this please and let me know. Oh, I hope you have XP, cause this is what I use to explain right now and I don;t remember the Vista settings, Vista is another kind of monster. Hope you find something. Cheers, Panoz