Vista x64 Harware or Software issue

Heres is my issue.
When adding a secondary hd to my system either internal or external the
system will not boot into windows. IT will post and the bios sees the
drive correctly.
It will not boot with the second drive added even into safe mode.
The drive checks good by checkdisk. it is formated. When in the
external case with the power off the system will boot all the way and
turning on the drive it will become recognized by windows.
Tried Windows repair and it found no error.

Is this a possible hardware failure or windows issue.
The system is SATA and there are 3 devices on the SATA connectors. The
main hd and two opticals.