The Río Grande de Zacapa is a river in Guatemala.

From its sources in the southern mountain range in the departments of Zacapa and Chiquimula, the river flows northwards until it reaches the Motagua River at 15°01′55″N 89°33′21″W / 15.032048°N 89.555826°W / 15.032048; -89.555826 (convergence Motagua river and Río Grande de Zacapa).

The Río Grande de Zacapa is 87 kilometres (54 mi) long and its river basin covers an area of 2,462 km² (951 sq ml).

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