The men were walking west on the train tracks near Ramseur and Roxboro streets when the accident happened around 4:15 p.m.
The conductor of a westbound Norfolk & Southern train told police he saw the two men on the tracks and blared the train's horn in warning several times, but the men did not move out of the way.
The two men, who have not been identified, were pronounced dead at the scene. No one on the train was injured.
"(The conductor) started blowing his horn and kept blowing his horn, hoping that they would hear it," police spokesman Norman Blake said. "By the time they realized the train was behind them, it was too late."
The train was traveling at about 30 miles per hour.
The accident left the mile-long train idle, blocking four intersections in downtown Durham and several main routes onto and off of the Durham Freeway.
The train started back on its way 9:30 p.m. Police said it may take some time to identify the victims.
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