Dr. Richard Kimble (Harrisson Ford), a successful vascular surgeon in Chicago, comes home one night to find his wife, Helen (Sela Ward), fatally wounded by a one-armed man, and though he attempts to subdue the killer, the man escapes. Earlier that night, Kimble and Helen were returning from a charity dinner. Kimble got a call on his car phone, regarding an emergency in surgery and he headed to the hospital to perform an operation on a trauma victim. When Kimble returns home, he sees the one-armed guy leaving and tries to stop him. Then he finds Helen lying on the floor and tries to move her, and she scratches his neck with her nails. Kimble prints are found on the lamp (used to crush her skull), the gun and the bullets (used to shoot her dead). The lack of evidence of a break-in, being the beneficiary of Helen's lucrative life insurance and a misunderstood 911 call (her skull was crushed when she made the call, and in her delusion she asks "Richard, is he trying to kill me", which is interpreted as Helen identifying her murderer as Richard Kimble) led to Kimble's being convicted of first-degree murder, for which he is sentenced to death. On his way to death row via bus, the other prisoners attempt an escape that wounds two guards (Richard Riehle & John M. Watson, Sr.) and kills the driver, causing the bus to fall into the path of an oncoming train. Kimble barely escapes the bus's destruction, saving the guard's (John M. Watson, Sr.) life by dragging him out of the bus. The train derails and coming right at Kimble, who is not able to run due to the chains in his feet. Kimble barely reaches the underside of a small railway bridge just as the train passes over him and crashes, causing widespread destruction. A fellow inmate, who had the keys, pulls Kimble out and gives him the keys to his shackles. Deputy Samuel Gerard (Tommy Lee Jones) and a group of US Marshals arrive, to locate and round up the escaped convicts while the injured are taken to a nearby hospital. Kimble sneaks into the same hospital to treat his wounds and change his appearance. Marshals include Deputy U.S. Marshal Cosmo Renfro (Joe Pantoliano), Bobby Biggs (Daniel Roebuck), Noah Newman (Tom Wood), Erin Poole (L. Scott Caldwell), Henry (Johnny Lee Davenport) and others. While leaving the hospital, he is recognized by the injured guard, but escapes in an ambulance. Gerard and his team blockade a tunnel through a nearby dam to stop Kimble's escape, but Kimble abandons the vehicle and climbs into the storm water system. Kimble is eventually cornered by Gerard above the outlet of the dam spillway. Kimble asserts his innocence, but Gerard responds that he does not care, and Kimble makes the dangerous jump into the waters below to escape. Kimble returns to Chicago to find the murderer and receives some money from his friend and associate, Dr. Charles Nichols (Jeroen Krabbe). Posing as a janitor, Kimble enters Cook County Hospital's prosthetic department to obtain a list of people who had their prosthetic arm repaired shortly after Kimble's wife's murder. After, he is asked to move a young patient on a gurney but, noticing he has been misdiagnosed, Kimble changes the boy's file, saving his life. A doctor notices his interference and alerts security, forcing Kimble to flee. Gerard realizes that Kimble must be looking for the one-armed man and begins a similar search to anticipate Kimble's next move. Kimble goes to the Cook County Jail to meet a one-armed man accused of armed robbery, but sees he is not the murderer. Gerard and his team also go to the jail with the same suspicion, and Gerard spots Kimble as he is leaving. A chase ensues, in which Gerard fires several shots at Kimble which are stopped by bulletproof glass. Gerard chases Kimble into Chicago's St. Patrick's Day parade where Kimble barely escapes. He then visits the home of the next person on the list, a former police officer named Frederick Sykes (Andreas Katsulas). Kimble confirms the man is the murderer. He discovers evidence linking Sykes to his former colleague, Dr. Alec Lentz (David Darlow), and Devlin-MacGregor, a multi-billion dollar pharmaceutical company developing a drug called Provasic Kimble had reviewed Provasic and found it caused liver damage, which would have prevented the drug being approved. He also finds that Nichols, who is leading the drug's development, arranged a cover-up, and ordered Sykes to kill Kimble (his wife's death was incidental). Kimble calls Gerard from Sykes's home to lead him there. Suspicious at what he finds, Gerard puts Sykes under surveillance, but he sneaks away. Conferring with another colleague, Kimble realizes that the Provasic-afflicted liver samples he sent to Lentz were tampered with to show no side-effects and approved in Lentz's name on the same day that he died in suspicious circumstances. Kimble deduces that Nichols, Lentz's boss, was responsible. Aboard a train to a medical conference in a hotel where Nichols will unveil Provasic, Kimble is attacked by Sykes, who shoots dead an intervening police officer. Kimble subdues and handcuffs Sykes to the train. The police assume Kimble killed the officer and order him shot on sight. At the conference, Kimble publicly confronts Nichols for killing Lentz and concealing Provasic's side effects for profit and a directorship at Devlin-MacGregor. The men fight through the hotel, across the roof, and into the laundry room, pursued by Gerard. Kimble accuses Nichols of sending Sykes to kill him for opposing Provasic, inadvertently resulting in Helen's murder as Kimble was unexpectedly called to work. Gerard calls out to Kimble, asserting his belief in his innocence after finding evidence of Nichols's guilt. Nichols knocks out Gerard's colleague, takes his gun, and readies to shoot Gerard, but Kimble saves him by attacking Nichols with a pipe. Kimble surrenders, and Sykes and Nichols are arrested. While the press query the police over failings in the case, Kimble is escorted to Gerard's car, where he reminds him of his earlier claim that he did not care. Gerard wryly asks Kimble to keep it a secret that he does.
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