The Río Grande (or Río Guapay) in Bolivia rises on the southern slope of the Sierra de Cochabamba, east of the city of Cochabamba, at 17°26′11″S, 65°52′22″W. At its source it is known as the Río Rocha and crosses the Cochabamba valley basin in a westerly direction. After 65 km the river turns southeast and after another 50 km joins the Río Arque at 17°42′10″S, 66°14′45″W and an elevation of 2.350 m.

From this junction the river is given the name Río Caine for 162 km and continues to flow in a southeasterly direction, before it is called Río Grande. After a total of 500 km the river turns northeast and in a wide curve flows round the lowland city of Santa Cruz.

After 1.438 km, the Río Grande joins the Río Ichilo at 15°48′09″S, 64°43′47″W which is a tributary to the Río Mamoré.