I have a XenApp 6.5 environment, that uses smart card authenication for login. All the office applications will open except for outlook. Outlook opens up and shows a prompt saying "Connecting" ...."Then server is unavailable".

If I removed the smart card authenication from the XenApp environment, User are able to open Outlook with no problem.

My question, is there something with exchange 2010 that needs to be turned on for smart card authenication?

Hi,

I suggest you remove any existing certificate-based credentials from the Credential Manager and use the EnableSmartCard registry setting to check the result. The Outlook client may not be properly configured to work with saved smart card credentials.

Important Follow the steps in this section carefully. Serious problems might occur if you modify the registry incorrectly. Before you modify it, back up the registry for restoration in case problems occur.

Remove existing certificate based credentials

The first step to prevent a PIN lockout is to delete any existing certificate based credentials that were saved by Outlook.

1. Open Control Panel.
2. Double-click Credential Manager.
3. See whether there is a Certificate-Based credential similar to the following:
   
   @@BSUgiZQZ54Pf6cEtxKflWHH
   
   Also, see whether there is a Generic credential similar to one of the following:
   
   MS.Outlook.14:user@domain.com:PUT
   MS.Outlook.15:user@domain.com:PUT
   
   Note 14 indicates Outlook 2010 saved the credential and 15 indicates Outlook 2013.
4. If these are both present and were created or changed at the same time, they are likely smart card credentials saved from Outlook. Click the first credential to expand it and to show the details. Then, click Remove to delete the credential from Credential Manager.
5. Repeat step 4 for each one of the credentials listed in step 3.
6. When you are finished, close Credential Manager.

Configure the EnableSmartCard registry setting

The second step to prevent a PIN lockout is to create the EnableSmartCard registry setting.

Outlook 2010

For Outlook 2010, the EnableSmartCard registry setting was introduced with the Microsoft Outlook 2010 hotfix package dated December 13, 2011 (KB2597028). We recommend that you install the most recent build of Outlook 2010. For more information about the latest applicable updates for Outlook, click the following article number to view the article in the Microsoft Knowledge Base: 2625547 How to install the latest applicable updates for Microsoft Outlook (US English only)
To create the EnableSmartCard registry value, follow these steps:

1. Exit Outlook.
2. Start Registry Editor.
3. Create the following registry values at the specified locations:
   
   Note Manually create any registry keys or values if they do not exist.
   
   Key: HKEY_CURRENT_USER\Software\Microsoft\Office\14.0\Outlook\RPC
   DWORD: EnableSmartCard
   Value: 1
4. Exit Registry Editor.

For this question, if you need to get more information about Exchange 2010, I suggest you post the question in Exchange forum:

https://social.technet.microsoft.com/Forums/exchange/en-US/home?category=exchangeserver

Regards,

Melon Chen
TechNet Community Support