The river creates a micro-region of Pčinja, with center being the municipal seat of Trgovište where Tripušnica meets the left tributary of the Lesnička River (Serbian: Лесничка Река, romanized: Lesnička Reka) from the south and continues to the west under the name of Pčinja.

The region represents one of the fastest depopulating and economically least developed parts of Serbia (population of 12,556 in 1971 (34 per km2) and 6,372 in 2002 (17 per km2; down 50%).

Just after the river passes next to the monastery, after 52 km of flow in Serbia, the Pčinja crosses the Macedonian border.

It passes next to the villages of Karlovce, Dragomance, Strnovac, Vojnik, Klečevce, Pčinja, Studena Bara, Gorno Konjare, Dolno Konjare and the small town of Katlanovo, with the neighboring Katlanovska Banja,[2] the most popular spa in North Macedonia.

Katlanovo is located on the Skopje–Thessaloniki highway, and even though some 25 km away from Skopje, a string of Skopje's fast growing suburbs is located along the highway (Jurumleri, Idrizovo, Petrovec), and if the city continues to grow, in some future it will reach Katlanovo and the banks of Pčinja.