Have you reached, or are you approaching your monthly upload limit? When annotating a PDF, the entire PDF is re-uploaded and counts against your limit. If the PDF is 3mb, and you make a change, its a new 3mb upload. Do that 6 times and you've got 18mb counted against your limit. How big is the PDF? how big is the note? (These can be seen in the header for the attached PDF, and the note information popover, respectively). Do either of these exceed the limits of your Evernote account? It could be a file permissions issue, perhaps the PDF is "locked" for some reason (I encounter this from time to time for a reason I cannot explain)What happens if you: 1) save the PDF back to your desktop. 2) try to modify and the PDF using Preview 3) If that works, create a NEW note in Evernote and attach the PDF to that note 4) try annotating the PDF again. If (2) doesn't work, it sounds like an issue of file permission, and not necessarily an Evernote issue. You can try saving a new copy of the PDF which might have more linnet and appropriate file permissions. Also, you say you click the "Annotate this note" icon. Why not click on the annotate button for the PDF itself (or right-click and select "Annotate this PDF")? Thanks for the suggestions, however I have a Premium account and am nowhere close to hitting the monthly limit. I'd also checked file permissions already, no issue there. Adding the markup in Preview then saving the pdf is my current workaround. Still can't annotate further in EN, regardless of which method I try. As the previous poster has written that EN have confirmed this is a known issue I'm going to log it with them as well, although given the length of time this has been outstanding I think it's time to look at alternative software too.