The city is located in the north-east of Buenos Aires (at 35°20′30″S, 60°12′8″W), 240 km from Buenos Aires City, within the so-called Industrial Corridor that goes from Greater Rosario to La Plata. Its limits are: to the west, Pergamino; to the south, Ramallo; to the east, with the Paraná River, which separates it from the province of Entre Ríos; and to the north, with the Arroyo del Medio, a small river that separates it from the province of Santa Fe.
Its main accesses are in the north-south axis: the Rosario-Buenos Aires Highway, and the Central Argentino Railroad.
San Nicolás has an important port on the Paraná, able to service large cargo ships. The railway system has passenger and cargo stations, the latter reaching up to the port.
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