The multi-vehicle crash happened on the northbound side of the Saw Mill River Parkway near McLean Avenue.
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.
Drivers are being told to avoid the area.
An investigation into the accident is ongoing.
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