Police said the buses on the Prithvi highway collided Monday near Simle village about 80 kilometers (50 miles) west of the capital, Katmandu.
The accident blocked the highway for several hours as tens of thousands of people are traveling during the biggest festival period celebrated in Nepal.
The highway is the main route linking Katmandu with rest of the country.
Nepal is celebrating a two-week long Dasain festival where people head home to celebrate with families.
Accidents in Nepal are generally blamed on poorly maintained roads and vehicles.
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