The central twist of "Once Upon a Time in America" is that Noodles' entire adult life has been shaped by a lie. The guilt he carries for 35 years over his betrayal—calling the police to prevent Max, Patsy, and Cockeye from undertaking a suicidal heist—is misplaced. In the film's 1968 timeline, Noodles discovers that Max was never killed. Instead, Max orchestrated the entire event, faking his own death, allowing Patsy and Cockeye to be killed, and stealing the gang's collective fortune to start a new life.
Noodles learns that Max reinvented himself as the powerful and wealthy Secretary Christopher Bailey, a prominent figure in the Teamsters Union. Furthermore, Deborah, Noodles' lifelong love, left him to become Bailey's mistress, and Bailey's son is the spitting image of a young Max. Max's motivation for this grand betrayal was his insatiable ambition; he saw Noodles as a sentimentalist who was holding him back from achieving true power. The invitation that brings Noodles back to New York was from Max himself. Facing ruin from a corruption scandal, Max wants Noodles to kill him, seeing it as a fitting, final act of revenge for the friend he destroyed.
Noodles refuses, poignantly telling Bailey, "You see, Mr. Secretary... I have a story also... Many years ago, I had a friend. I turned him in to save his life, but he was killed... It was a great friendship. But it went bad for him, and it went bad for me too." By refusing to acknowledge Bailey as Max and by refusing the contract, Noodles denies Max his desired end and preserves his own memories, however painful. He leaves the mansion, and Max walks out to an ambiguous fate involving a garbage truck, seemingly committing suicide.
The film's final shot returns to Noodles in the opium den in 1933, smiling blissfully. This makes the entire 1968 sequence—and its revelations—profoundly ambiguous. It can be interpreted as an opium dream, Noodles' subconscious constructing a narrative where he is the betrayed victim rather than the guilty betrayer, thus absolving himself and finding a twisted form of peace. Whether real or imagined, the truth Noodles uncovers is that his life of regret was built on the ultimate act of treachery by the person he trusted most.