Background: In an earlier analysis of this cohort study, local therapy based on surgical resection of the primary tumor might confer a survival benefit in women with de novo metastatic breast cancer (dnMBC). Here we report the survival outcomes of locoregional treatment (LRT), focusing on the association of surgical timings and surgical margins with survival in these patients. Methods: The retrospective study included patients with dnMBC in two Chinese tertiary hospitals, between March 1, 2007, and December 31, 2017. Overall survival (OS) was evaluated by means of a stratified log-rank test and summarized with the use of Kaplan–Meier methods. Results: A total of 153 patients were included, of whom 87 underwent LRT and 66 systemic therapy alone (STA). LRT showed a significant OS benefit over STA (HR, 0.47; 95% CI, 0.33 to 0.69; p<.0001). Median OS of LRT group and STA group were 42 months (95% CI, 35.0 to 48.9 months) and 21 months (95% CI, 16.1 to 25.9 months), respectively. The benefit was consistent across most subgroups. The OS of patients undergoing surgery was better than that of patients without surgery (HR, 0.48; 95% CI, 0.33 to 0.70; p=.0001), and there was difference in survival improvement at different surgical timings (surgery before chemotherapy, during chemotherapy and after chemotherapy) (HR, 0.79; 95% CI, 0.65 to 0.95; p=.013). The survival benefit of surgery after chemotherapy was the most, followed by surgery during chemotherapy (Median 56 months, 95% CI, 40.8 to 71.2 months). Moreover, compared with patients with positive margins, the OS of patients with negative margins was significantly improved (HR, 2.35; 95% CI, 1.65 to 3.35; p<.0001), with a median OS of 56 months (95% CI, 45.9 to 66.1 months). Conclusions: Our results suggest that LRT is associated with improved OS in women with dnMBC, and patients who had surgery after or during systemic chemotherapy with negative surgical margins, are expected to benefit more.