The Río Grande (or Río Guapay) in Bolivia rises on the southern slope of the Cochabamba mountains, east of the city Cochabamba, at 17°26′11″S 65°52′22″W / 17.43639°S 65.87278°W / -17.43639; -65.87278.

It crosses the Cochabamba valley basin in a westerly direction, turning south east after 65 kilometres (40 mi) and after another 50 km (31 mi) joining the Arque River at 17°42′10″S 66°14′45″W / 17.70278°S 66.24583°W / -17.70278; -66.24583 and an elevation of 2,350 m (7,710 ft).

From this junction the river receives the name Caine River for 162 km (101 mi) and continues to flow in a south easterly direction, before it is called Río Grande.

After a total of 500 km (310 mi) the river turns north east and in a wide curve flows round the lowland city of Santa Cruz.

After 1,438 km (894 mi), the Río Grande joins the Ichilo River at 15°48′09″S 64°43′47″W / 15.80250°S 64.72972°W / -15.80250; -64.72972 which is a tributary to the Mamoré.