In reply to:
Could it have been something to do with Terry? An intensely personal situation.
I agree, gouster.
To figure out what Bowie thinks was his No. 1 mistake, we have to consider the time he made the statement that marrying Angie was his No. 2 mistake. Yes, it was around the time he was turning 50. So more recent events like the heart scare could not have factored in to have him think, at that time, that starting to smoke was his biggest mistake. I don't even think he had entertained thoughts of quitting that habit at that time. He may view the smoking differently now, but that statement wasn't made after the heart scare, it was before it.
As for drugs, again, he may view the addiction differently now, but most people who abuse drugs and somehow miraculously survive events that end up killing many of their friends who did the same things don't, on balance, feel "regret" for their drug use. They acknowledge that some good things came of it, and feel they would not have avoided drugs entirely if they got the chance to do it all over again--for fear that by eliminating the bad (drug use), they would end up unraveling some of the inextricably intertwined good (e.g., inventive, groundbreaking music) that also stemmed from the drug (ab)use.
So . . . that leaves me voting with gouster, and saying that, in 1997, Bowie viewed something connected to Terry as his "biggest mistake."
Another candidate for "biggest mistake" may have been not being there when his father took ill. Didn't Stenton die of pneumonia in part because David's mother did not call the doctors in time? Now David's mother was not a certifiable, labotomized mental health patient (like many of David's other relatives from his mother's side), but what I know of her suggests she was perhaps manic depressive, just plain depressed, or otherwise in some mental distress. Perhaps David regrets entrusting his mother to ensure his father would be o.k. It is clear he was closer to his father than his distant and often disapproving mother. And his father was supportive of David's musical aspirations. Perhaps in some way, whether valid or not, he feels responsible for his father's death because he should have known better than to trust his mother's judgment when his father fell ill.
Despite how much DeFries may have ripped off from Bowie, I simply can't imagine that as Bowie was nearing 50, feeling still invincible (remember, it was pre-heart attack), being wealthy as shit, and happily married (and, according to many reports, he and Iman were already desperately trying to conceive and start a family), and still seething over Tony Fucking DeFries. I would be shocked if he ever felt his "biggest mistake" was career- or money-related.