See also Why I Use Three NEC Displays on Mac Pro.
I was having so many problems with a 3rd display going AWOL that I gave up on it several weeks ago; it was just too flaky. Often the 3rd display (4K) would not sync up at all, even after a reboot (and particularly after sleep).
The OS X 10.11.3 release notes are terse, but one note states*:
Fixes an issue that may prevent some Mac computers from waking from sleep when connected to certain 4K displays.
The fix seems to work: I can now use three displays and have them all sync up and wake up from sleep properly.
The wakeup process is an inelegant herky-jerky multi-step process: the main display comes back and sometimes the 2nd too, but then there is a 10-15 second series of screen blanks and resyncs until all three displays are finally back—all good in the end but unusable during that restoration period.
Because of the discombobulated wakeup process, windows from the 3rd display are forced onto the main display during the process, because the 3rd display is not yet present (standard behavior when a display goes offline). So windows for the 3rd display have to be moved back manually, which is annoying. But at least all three displays come back alive and working correctly after sleep or reboot.
Update 1: all was well for a few days. Then upon wake-from-sleep one morning, the 3rd display was set to some smeared mode, and after that it was back to flaky wakeups all over again, even after forcing the screen resolution to the correct setting. Looks like Apple HAS NOT fixed the bugs.
Update 2: not only are the bugs not fixed, but things are now worse with 10.11.3. Having abandonded a 3rd screen as too unreliable, even a 2nd direct-connect display now often will not come back online after sleep. Symptoms are that the system sees the screen as there, but it remains black.
Update 3, Apr 8: OS X 10.11.4 appears to have resolved the 2-display problem(previous update). MPG has not been tempted to try 3 displays again—let sleeping dogs lie.
Gross incompetence is at work here, including making the iMac 5K with its single built-in display fail after sleep.
* Incorrectly mixed verb tenses never inspire confidence (“Fixes an issue that prevented...”).