The highway has been closed after the accidents.
Police said 16 people died when a speeding truck collided head-on with a car on NH-34 at Kaluadighi near Malda town while two others were killed when their vegetable-laden pick-up van rammed into a stationary truck at Gajol in the district.
Fifteen men and a child were among those killed in the first accident which took place about 7:30 AM at Kaluadighi, police said.
While 13 people died on the spot, three others died after being taken to Malda Medical College and Hospital, officials said.
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State government has declared Rs 2 lakh as compensation to the families of each of the 16 dead people in the accident, District Magistrate Sarat Kumar Dwivedi said.
In the second accident, two people died when their vegetable-laden van hit a standing truck on NH-34 at Alampur in Gajol police station in the district.
Two others, who were injured, have been admitted to a local hospital.