User blog comment:Putowtin/Commander Shepherd Can Lose in Mass Effect 3/@comment-1388547-20110827162629

Sounds reasonable. I expect BioWare will want to leave the ME galaxy in a usable state after the end of ME3 (they've built a big, exciting world -- they'll probably want to keep cashing in on it with more games), but I've wondered if they might do some kind of creepy mind screw thing like including the possibility that the Reapers win at the end of ME3 and events of subsequent games in the franchise take place inside a Reaper simulation.

I wouldn't anticipate players to be completely locked out of a happy ending in ME3 based on decisions made in the previous games, but it sounds reasonable to have it possible to fail to save the galaxy based on decisions within ME3. (The consequences had better be obvious ahead of time, though!) The same would probably go for Shepard dying -- if the right decisions aren't made, Shepard might have to sacrifice him/herself to save the galaxy, though I'd also hope that this is something that only hinges on ME3 decisions. Having the "best ending," though, would probably depend on the decisions you've made throughout the series. (As an aside, I hope there's both a Paragon and a Renegade "best ending," perhaps with a Paragon Shepard uniting the galaxy in peace, with all species surviving only a little worse for wear, and a Renegade Shepard using the other species as cannon fodder and putting humanity in a position of unquestioned dominance.)