I had previously installed the VS11 beta, and had some issues with my Visual Studio 2010 instance, which you can see here how they were resolved: Excel AddIn Click Once deployment issue.
Now I have a code base which compiles/builds a vsto, which installs fine and runs fine in Excel 2010. However, when I remove the installed version from Excel, and try to run it directly through Visual Studio 2010, the AddIn does not get loaded into Excel when running in debug configuration mode, in release configuration mode it works fine. Any ideas on why this might be occurring? I've tried re-enabling it through Com AddIns, and a few other things with no luck.
I've found the issue which was not letting me run my project in 'Debug' configuration mode, though it worked in 'Release' mode. At some point, the AddIn, got hard-disabled (not sure if that's the term to use). At that point, trying to re-enable from within Excel doesn't do anything. Within the registry, there is a folder where disabled AddIns are flagged. I deleted all of the keys from this folder except for "(Default)" and now my AddIn works when launching from Visual Studio 2010 in 'Debug' mode.
HKEY_CURRENT_USER\Software\Microsoft\Office\14.0\Excel\Resiliency\DisabledItems
When you run through Visual Studio 2010 does it hits the breakpoint in the addin_startup event. If not try to debug this way
Hope this helps you
You can reenable a hard-disabled Add-In with Excel
http://msdn.microsoft.com/en-us/library/ms268871(v=vs.80).aspx
I had the same problem with a Word VSTO, but there was no Resiliency\DisabledItems folder in my registry, so I think it was never hard disabled (as in @mservidio's solution). What worked for me was to edit the Manifest path in HKEY_USERS\<user key>\Software\Microsoft\Office\Word\Addins\<Add-In name> to reflect the 'Debug' path rather than the 'Release' path.
To find the right folder it might be easiest just searching for the Add-In name and checking that any Manifest keys refer to the Debug path.
I had the same problem in Excel.
The following worked for me:
Go to the following key....
HKEY_CURRENT_USER\Software\Microsoft\Office\15.0\Excel\AddInLoadTimes
see if your plug-in is listed. if so, delete it.
now run your app from Visual studio again.
This worked for me, hope it can help someone else.
I also had the same problem, what I didn't understand was :
Why I re-install Office 2016, I don't change my code neither VS setting but I get a cant load error message ?
After many many hours, repairing Office and VS and getting the same error message, I observed that the Addin was starting well in Release config, I started checking the difference between the both config in my code.
I found that debug config was targeting to x86 proc bug release to any cpu
So Office x64 didn't load x86 dlls (in my case)
来源：https://stackoverflow.com/questions/10287007/excel-wont-open-launch-vsto-addin-when-running-in-debug-mode-of-visual-studio-2