The multi-vehicle crash happened on the northbound side of the Saw Mill River Parkway near McLean Avenue.
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Westchester County Police say two people were killed in the crash and three others were injured.
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According to a preliminary investigation, a Lincoln SUV was traveling southbound on the parkway and lost control, went through an opening in the center median's concrete divider, and collided with a Hyundai SUV traveling northbound.
The driver of the Lincoln, 57-year-old Adolph Cintron Jr., of Brooklyn, was killed, along with the driver of the Hyundai, 40-year-old Noe Perez Procopio, of the Bronx.
Perez Procopio's wife and teenage daughter were injured but expected to survive.
In addition, the driver of a third vehicle that was also traveling northbound was injured when a secondary crash occurred after the initial accident.
The northbound lanes were closed much of the afternoon due to the investigation and part of the southbound side has also been closed.
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Drivers are being told to avoid the area.
An investigation into the accident is ongoing.
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