Background: Inflammatory breast cancer (IBC) is a rare and highly aggressive subtype characterized by rapidly progressing breast erythema, tenderness, enlargement, induration, and warmth. NCCN guidelines recommend trimodality treatment for patients diagnosed with IBC: neoadjuvant chemotherapy, modified radical mastectomy, and chest wall and regional nodal radiation therapy. This multidisciplinary approach has improved survival rates for patients with IBC. In spite of aggressive therapies, however, patients with IBC still face a poor prognosis. Patients and methods: This is an IRB approved retrospective review of patients diagnosed with IBC between 2008 and 2018 at an NCI-designated comprehensive cancer center. We compared the clinical characteristics, treatment regimens, and survival outcomes between non-metastatic IBC patients and comprehensively matched patients with stage III invasive non-IBC based on age, stage, and biomarker status. Results: A total of 165 patients (84 IBC, 81 non-IBC) were eligible for analysis. The median age at diagnosis was 53 years (range 29 - 76) and the majority of the cancers were estrogen receptor negative (92, 55.8%), progesterone receptor negative (106, 64.2%), human epidermal growth factor receptor 2 negative (98, 59.4%) and high grade (106, 64.2%). Overall survival, disease-free survival, and distant disease-free survival were statistically significantly lower among patients with IBC (log-rank test, p-values: 0.008, 0.001, and 0.02, respectively) as seen in the figures. There was no statistically significant difference in pathologic complete response rates between cohorts (Fisher’s exact test, p = 0.88). Comparison of prognostic factors between cohorts indicates that age is a negative predictor for overall survival (HR 1.44 per 10 years, 95% CI = 1.15 to 1.81, p = 0.009), disease-free survival (HR 1.32 per 10 years, 95% CI = 1.06 to 1.64, p = 0.05), and distant-disease free survival (HR 1.28 per 10 years, 95% CI = 1.04 to 1.58, p = 0.04). Receipt of neoadjuvant chemotherapy was associated with enhanced distant disease-free survival (HR 0.45, 95% CI = 0.23 to 0.87, p = 0.02) and there were trends towards improved overall and disease-free survival which did not rise to statistical significance. Conclusion: Our study revealed worse outcomes for patients diagnosed with IBC than matched patients with non-IBC. We also demonstrated a trend toward improved outcomes for IBC patients treated with neoadjuvant chemotherapy.