Why can't Alteryx read in Excel files that are open?
The best answer to this question comes from @MikeBas posted as a response in the discussion boards. His answer in full is shown below:
The reason we can't read an Excel file when it is open is because Excel puts a write lock on the file. We also decided that reading an open file has challenges like what happens if the file is modified and saved while we are reading it? To avoid those and other edge cases, we made the decision to limit reading and writing Excel files to those that are not currently locked. You can open your file in Excel for "Read Only" and then Alteryx can read the file without any problem.
That said, if you install the Microsoft Access 2010 driver you will be able to use that driver which can read and write to open Excel files. In Alteryx it's called the Excel Legacy driver. However, be aware that if you use the Access driver you may get different results (rounding) depending on whether the file is currently open in Excel or not. The Access driver uses a 2nd library that allows reading and writing to an open file (open with a write lock). The 2nd driver does rounding slightly different from the main driver that is used if the file is not open.
If those limitations are not a problem for you, I'd suggest trying the Access driver which you can download here:
If you have 32bit Office installed, it's suggested that you go with the 32bit version of this driver. If 64bit Office, then go with the 64bit version.
Then in Alteryx choose the Excel Legacy format (this format will appear once the driver is installed).
NOTE: This driver was delivered with Office 2010, but is missing from later versions of Office. So if you are running a later version of Office, you'll need to install it yourself.
Hope this helps.