Abstract Introduction: Inflammatory breast cancer (IBC) is an aggressive breast cancer subtype with poor prognosis. In the non-metastatic setting, the current literature suggests modified radical mastectomy (MRM) in conjunction with chemotherapy and radiation therapy improve clinical outcomes. However, for de novo metastatic IBC patients, surgical management is mostly palliative, and little is known about its implications for survival. The objective of this study is to evaluate the association between MRM and disease specific survival (DSS) among a contemporary cohort of de novo stage IV IBC patients. Methods: The Surveillance, Epidemiology and End Results (SEER) Program was queried for IBC (T4d) patients diagnosed between 2010-2016. The study cohort was divided into two groups- MRM vs no MRM. Surgical management was limited to patients who underwent MRM. Bivariable analysis was conducted to compare sociodemographic and clinical variables between the groups. The surgery group was nearest matched to the no-surgery group (1:2) on age, year of diagnosis, location of metastasis (e.g., bone only), number of metastatic sites, breast cancer subtype, chemotherapy and radiation therapy. A Kaplan-Meier curve was used to evaluate DSS between the two groups in the matched sample. Results: Of the 1293 patients who met study criteria, 240 underwent MRM and 1053 had no surgery. Patients undergoing MRM were more likely to be younger (MRM 55.7years±13.5, no MRM 59.40years±13.4; p<0.001), have poorly differentiated tumors (grade 3; MRM 63.7%, no MRM 46.7%; p<0.001) and metastasis in only one organ site (MRM 69.8%, no MRM 52.2%; p<0.001). On matched analysis, patients who underwent MRM had longer DSS than those who did not undergo surgery (p=0.001). Moreover, the 5-year survival rate for surgical patients was 31.4% compared to 17.7% for the no surgery group. The median survival time was 38 months for patients who underwent MRM (interquartile range [IQR] 27-45 months] compared to 27 months (22-29 months) among those who did not have surgery. Conclusion: In this SEER cohort of de novo metastatic IBC patients, MRM was associated with an improved disease specific survival compared to no surgery. These results suggest surgical management should be considered in this population. Future prospective studies are needed to better define which subset of de novo metastatic IBC patients derive the most benefit from surgery, and consequently, should routinely undergo surgery. Citation Format: JC Chen, Yaming Li, James L. Fisher, Allan Tsung, Samilia Obeng-Gyasi. Does modified radical mastectomy in de novo stage IV inflammatory breast cancer patients improve disease specific survival? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-24-01.