Background: It remains controversial whether palliative primary tumor resection (PPTR) can provide survival benefits to the patients with metastatic colorectal cancer (mCRC) who have unresectable metastases. The aim of this study was to evaluate whether PPTR could improve the survival of patients with mCRC. Methods: We conducted a retrospective study on consecutive mCRC patients with unresectable metastases who were diagnosed at Sun Yat?sen University Cancer Center in Guangzhou, Guangdong, China, between January 2005 and December 2012. Overall survival (OS) and progression?free survival (PFS) after first?line chemotherapy failure were compared between the PPTR and non?PPTR patient groups. Results: A total of 387 patients were identified, including 254 who underwent PPTR and 133 who did not. The median OS of the PPTR and non?PPTR groups was 20.8 and 14.8 months (P < 0.001), respectively. The median PFS after first?line chemotherapy was 7.3 and 4.8 months (P < 0.001) in the PPTR and non?PPTR groups, respectively. A larger proportion of patients in the PPTR group (219 of 254, 86.2%) showed local progression compared with that of patients in the non?PPTR group (95 of 133, 71.4%; P < 0.001). Only patients with normal lactate dehydrogenase (LDH) levels and with carcinoembryonic antigen (CEA) levels <70 ng/mL benefited from PPTR (median OS, 22.2 months for the PPTR group and 16.2 months for the non?PPTR group; P < 0.001). Conclusions: For mCRC patients with unresectable metastases, PPTR can improve OS and PFS after first?line chemo?therapy and decrease the incidence of new organ involvement. However, PPTR should be recommended only for patients with normal LDH levels and with CEA levels <70 ng/mL.