The 16th International 500-Mile Sweepstakes Race was held at the Indianapolis Motor Speedway on Wednesday, May 30, 1928. This was the first Indianapolis 500 presided over by new Speedway president Eddie Rickenbacker. Rain threatened to wash out the day, but the showers stopped and the race started on time. One brief shower slowed the race around the 400-mile mark, bringing out the yellow flag for a few laps.

It was the third year contested with the supercharged 91 ¹⁄₂ cu. in. (1.5 L) displacement engine formula. A total of seven supercharged front-wheel drive cars were entered, and they swept the front row during time trials. Leon Duray in a Miller took the pole position with an average speed of 122.391 mph (196.969 km/h), a new track record. Duray dominated much of the first half of the race, setting a blistering pace. He dropped out in the second half, however, due to an overheating engine.

With twenty laps to go, Tony Gulotta led Jimmy Gleason and Louis Meyer. All three cars were running nose-to-tail. On lap 181, Gulotta slowed with a leaking fuel tank and a clogged fuel line. Gleason and Meyer then battled for the lead. On lap 196 Gleason headed for the pits to take on water for the radiator. A crew member missed the radiator and accidentally doused the car's magneto with water. The engine was ruined with a cracked water jacket in sight of victory.

Rookie driver Louis Meyer (though he had appeared as a relief driver in 1927) took the first of what would be three career Indy victories. Meyer did not even land his ride until one week before the race. Car owner Phil "Red" Shafer entered a rear-wheel drive Miller Special for Wilbur Shaw with initial backing from a fuel pump manufacturer. The deal fell through, and Shafer abruptly sold the car to Alden Sampson II four days before time trials were scheduled to begin. Sampson hired Louis Meyer to drive the car, the same machine that Tony Gulotta drove to a third place in 1927. Meyer put the car safely in the field in 13th starting position. He drove a steady, consistent pace, and led only once, the final 19 laps of the race. Despite predictions of record speed, and an early blistering pace, Meyer's average speed of 99.482 mph for the 500 miles fell short of the record set in 1926.

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