The 65th Indianapolis 500 was held at the Indianapolis Motor Speedway in Speedway, Indiana on Sunday, May 24, 1981. The race is widely considered one of the most controversial races in Indy history.Bobby Unser took the checkered flag as the winner, with Mario Andretti second. After the conclusion of the race, USAC officials ruled that Unser had passed cars illegally while exiting the pit area during a caution on lap 149. Unser was subsequently issued a one-position penalty. The next morning, the official race results were posted, and Unser was dropped to second place. Mario Andretti was elevated to first place and declared the race winner.

After a lengthy protest and appeals process, the penalty was rescinded, and Unser was reinstated the victory on October 9. Officially, it became Unser's third-career Indy 500 victory and his final win in Indy car competition. Unser stepped out of the car at the end of the season, and ultimately retired from driving.

The race was officially part of the 1981–82 USAC season. However, most of the top entrants participated in the 1981 CART PPG Indy Car World Series. Championship points for the 1981 Indy 500 were not awarded towards the CART title.

The hectic month of May 1981 was interrupted several times by rain. Pole qualifying stretched over three days due to inclement weather, and several days of practice were cut short or lost due to rain. The 1981 race is also remembered for the horrifying crash of Danny Ongais, and a major pit fire involving Rick Mears. Ongais was seriously injured, and Mears suffered burns, but both drivers would recover. Another major pit fire occurred later in the season at the Michigan 500, prompting new rules and standards to be put in place regarding the safety of fueling rigs.

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