Om Prakash Makhija (Shah Rukh Khan) is a junior artist in the 1970s Hindi film industry, in love with film star Shanti Priya (Deepika Padukone). One evening, Om views the premiere of Shanti's film Dream Girl, posing asManoj Kumar. Later that night, Om becomes drunk and describes his vision of himself as a famous, wealthy film star wining the Filmfare Award for Best Actor to his friend Pappu (Shreyas Talpade) and some local children. At the shooting of a later film, Om rescues Shanti from a fire scene where of the fire has escaped control, and they become friends. One day, after following Shanti, he overhears her and producer Mukesh Mehra's (Arjun Rampal) conversation, that Mukesh and Shanti have married in secret and Shanti is pregnant and expects a traditional wedding. Mukesh pretends to be happy with the news, and invites Shanti at the set of their soon-to-be-made film Om Shanti Om. Mukesh promises to cancel the film, reveal their marriage to the public, and have a grand wedding on the set; but instead traps Shanti on the set and sets it on fire to prevent his financial loss and downfall of his career.

Om, who happens to be at the same location that night, attempts to rescue Shanti, but is attacked by Mukesh's guards, and later thrown from the building by an explosion. Outside, Om is hit by a car owned by Rajesh Kapoor (Javed Sheikh), a well-known actor taking his wife Lovely to the hospital to give birth. At the hospital Om succumbs to his injuries, while Lovely gives birth to a son, also named Om, who in adulthood becomes a popular movie star and a lookalike of Om, nicknamed 'O.K.', and lives the luxurious life imagined by Om Prakash, but experiences pyrophobia and subconsciously inherits Om Prakash's memories. In acceptance of an award, O.K. unexpectedly delivers Om Prakash's drunken speech to the assembly. Pappu hears this on television. At a celebration of his award, O.K. is introduced by his father to Mukesh Mehra, and thereupon completely recovers Om Prakash's memories. He later reunites with Om's mother Bela (Kirron Kher) and Pappu and conspires to avenge Shanti's death by making Mukesh confess his crime. To that end, O.K. convinces Mukesh to restart Om Shanti Om, while scheming to convince Mukesh that Shanti is a ghost haunting himself. To impersonate Shanti, O.K. finds Sandhya, a.k.a. Sandy, a doppelganger of Shanti. Throughout the film's shooting, O.K. and his friends arrange incidents to remind Mukesh of his crime. During the music launch of the film, O.K. taunts Mukesh by revealing, through a song, the extent to which he knows the story of Shanti's death. Seeing Sandy bleed of a scratch, Mukesh confirms that she is not Shanti's ghost. Thereafter O.K. and Mukesh confront each other with their knowledge of each other's actions. During the quarrel, an apparently-genuine ghost of Shanti reveals that Mukesh, after the fire ceased to burn, buried her alive below the set's chandelier. Mukesh attempts to shoot the ghost, shocked by the extent to which she knows about the murder, but Mukesh and O.K. fight, which results in yet another fire; and the chandelier falls on Mukesh, killing him instantly. Pappu and Sandy join O.K. O.K. is shocked that he saw the same person and realizes it is Shanti's ghost. The ghost tearfully bids goodbye to Om. The film ends with Shanti's ghost leaving the scene and disappears in the light.

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