Works well for me

Im using a Wacom tablet and am on OS X 10.7 Lion and its working for me in Mail. Havent tried it elsewhere yet.
I assigned the key shortcut to invoke Autograph to my upper Wacom pen button in Wacom prefs specific to Mail.app and assigned the Return key to the bottom pen button so when Im done signing I hit the bottom pen button and it puts the signature in the email.
I hope you can get it working with PDFs!

Ratz2 about Autograph