Is there a setting I could change when opening a pdf to open in its own separate window rather than another tab in Preview?

I think you have to turn that off for all.

Desktop & Dock System Settings > Windows > Prefer tabs when opening documents : Never.

There is a similar setting for Image files in the Preview Settings, but I don't think that it applies to PDFs.

FaceTimeChallenges wrote:

Is there a setting I could change when opening a pdf to open in its own separate window rather than another tab in Preview?

There is not. There is no reliable way to get Preview to open files in any particular fashion. Even when you want them to open all in the same window, you may have to try it a couple of times to get it to work. If you want it to always work in the other direction, then forget it. A single window is how iOS is designed to work. As Apple transition the Mac to iOS, separate windows will become more and more difficult to use until they work exactly like they do on the iPad.

Old Toad wrote:

I'm able to get Preview to work with whatever open setting I choose reliably:

I keep forgetting about those settings. The first option, "open all files in one window" definitely doesn't work. However, whatever bug it is that prevents this setting from working shouldn't affect the opposite "open each image in its own window" setting. Thanks for pointing it out.

I'm able to get Preview to work with whatever open setting I choose reliably:

I don't need to restart Preview to change that particular setting. I'm on Ventura 13.6.5.

Give this a try: boot into Safe Mode according to How to use safe mode on your Mac and test to see if the problem persists. Reboot normally and test again.

NOTE 1: Safe Mode boot can take up to 3 - 5 minutes as it's doing the following; 

• Verifies your startup disk and attempts to repair directory issues, if needed

• Loads only required kernel extensions (prevents 3rd party kernel/extensions from loading)

• Prevents Startup Items and Login Items from opening automatically

• Disables user-installed fonts 

• Deletes font caches, kernel cache, and other system cache files

NOTE 2: if you have a wireless keyboard with rechargeable batteries connect it with its charging cable before booting into Safe Mode. This makes it act as a wired keyboard as will insure a successful boot into Safe Mode.

Have you installed and run any "cleaning", "optimizing", "speed-up", anti-virus or VPN apps on your Mac?

FaceTimeChallenges wrote:

Thanks for the effort, but I've tried that pathway and unless it is a change that requires restart to activate (because when I tried it there was no impact) I don't believe that's a solution to my problem. It's a "feature" of the new OS. But I just hate it!

It worked when I tested.

I have the same issue as the OP. Sometimes when I double-click on a PDF file it just opens into another tab in an existing Preview window, other times it will open in its own window. It is definitely annoying. I only started to notice this with macOS 11.x+. My Preview settings are the same as shown by @Old Toad even though that is under the "Images" tab.

I wasn't aware of the System Setting you mentioned earlier, so I will try that to see what happens.