Background: Pazopanib is approved for second or later line therapy for advanced soft tissue sarcoma (STS). Whether or not Pazopanib and radiation have cooperative effect remains unclear. Methods: We retrospectively reviewed 10 patients with locally advanced or metastatic soft tissue sarcoma treated with pazopanib either at the start of radiation or within 4 weeks after the start of radiation. Results: Seven patients were females and age ranged 39-80. Four patients had undifferentiated pleomorphic sarcoma (UPS), two leiomyosarcoma (LMS), two synovial sarcoma (SS), and two dedifferentiated liposarcoma (DDLS). All patients had a large primary tumor that was unresectable with or without distant metastasis. The disease burden with the distant metastasis was low for patients with metastatic disease. Radiation was delivered to the large primary tumor with dose ranging from 15 to 50 Gy (median dose 30 Gy). Pazopanib dose ranged from 400 to 800 mg (majority received 600-800 mg). Eight patients had received one to two lines of chemotherapy previously. Three patients whose pazopanib treatment is still ongoing with stable disease (SD) at 4 (UPS), 25 (LMS), and 26 (DDLS) months respectively. One patient (UPS) with SD discontinued Pazopanib after 3.5 months due to liver toxicities. One patient with SS obtained PR that lasted for 11 months and one patient with SS had SD for 12 months. One patient with relapsed abdominal DDLS obtained a PR followed by resection of residual tumor 8 months after the start of Pazopanib, however, disease relapsed again 3 months after the resection. Three other patients had SD for 8, 8 and 13 months respectively. Conclusions: Our results suggest that Pazopanib at the start or within 4 weeks of radiation in palliative dose can achieve prolonged disease control for patients with locally advanced or metastatic STS. This approach can be considered for selective STS patients with large primary tumor and low distant disease burden.