The answer is yes. Over and over on podcasts and forums, you can see experienced independant RPG publishers talking about how painful the process of publishing really is. This post in an anecdote.
I was midway through my first series of DL-Quarterly. I had sent the PDF files of "Standoff!" to my printer, RapidPOD. RapidPOD was local for me. It is headquartered in Brandenburgh Kentucky, which is only a few minutes drive from where I live. I want to help the entreprenuers in my state, so I decided to work with them. The first two books, Cutthroat and Hierarchy came back fine. Shipping seemed a little slow, but I was ahead of my deadlines which made everything work out okay.
The PDF for Standoff! was a little complicated. I had very narrow margins, the book cover was mainly a big red rectangle, and I used some pretty wierd fonts. It wasn't anything a print on demand printer couldn't handle, though.
I submitted my book in April, expecing to get it back in June at the latest- plenty of time to get it before GenCon. I got a confirmation email when I uploaded the file to their site, and I thought everything was cool. I was just starting on my Master's degree and the end of the school year was coming up, so I was focussed on creating my final exams and finalizing my students' grades. You know, teacher stuff.
Anyway, June rolls by before I know it. I give the printer a call, and it turns out my file has been lost. So I upload it again, somewhat worried about getting to GenCon this year with my games. A couple more weeks pass, and I call again. RapidPod was going through some sort of management change and it might be a while before I got my books, but I was assured they'd arrive prior to GenCon which was toward the middle of August that year.
August comes. I get a box on my porch. I now what it is, and I'm relieved. I take it inside and open it up with my wife to find that all of the books are horribly miscut. The covers are nearly diagonal. Words are chopped off on half the pages and a bunch of the icons didn't print. I call up RapidPod (now Vixen Printing) and complain. They offer to resend my order, but state that from now on I'd have to order a minimum of 100 books. I was irate.
I didn't go to GenCon that year. My books arrived four weeks later. I switched printers for The Holmes and Watson Committee and finished up the first series for DL Quarterly. Then I just shut the whole thing down. The experience really turned me off from publishing for a long time. I know many have had to go through the same thing.
Don't go into this thinking it's easy. I'm proud of the work I did with Divine Legacy and my earlier work with Twilight Press. In the end, it was all worth it. I'd do it all over again without a second though. But that doesn't mean it wasn't painful. It was.