If Mass Effect 2 could be possible that Commander Shepard dies in the last mission against the collectors, Mass Effect 3 will not be outdone and, indeed, may be far more catastrophic. In an interview with the site Nowgamer Mike Gamble, BioWare community manager, has confirmed that even in this third installment Shepard may not be able to stop the Reaper, bringing the total destruction of the universe.

The operation's success will be guaranteed only if all races and species of the Universe will be cohesive in the last battle: If the combined forces will not be sufficient or whether some of the races do not participate in the final conflict because of our actions, the odds that the enemies will go win. Then prepare ourselves to meet the various demands of the inhabitants of the universe and not to disappoint them, because unity is strength always.