It rises on the southern slopes of Gissar Range in Vahdat district, formerly Kofarnihon district, and flows for about 400 km in the general south-western direction past the cities of Kofarnihon, Vahdat, and Dushanbe, where it turns south and runs through Khatlon Province toward the border with Afghanistan.
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It is near several rivers, Shirkent and Karatag immediately to the west and east of the city, and Kofarnihon further east.