Background: Despite the established guidelines for breast cancer treatment, there is still variability in surgical treatment after neoadjuvant therapy among women with large breast tumors, leading to variability in the outcome. Our objective was to identify possible predictors of the type of surgical treatment; mastectomy versus breast conserving surgery (BCS) in women with T3/T4 breast cancer who received neoadjuvant therapy. Methods: Population-based Florida Cancer Registry and U.S. Census from 1996 to 2009 were linked to select women diagnosed with T3/T4 breast cancer who then received neoadjuvant therapy followed by BCS or mastectomy. A multivariable logistic regression model was used to identify significant predictors of type of surgery by including sociodemographic characteristics (race, ethnicity, socioeconomic status, age, marital status, urban/rural residency), tumor characteristics (ER/PR status, histology, grade, SEER stage, regional nodes positivity), treatment facilities (hospital volume, teaching/non-teaching), comorbidities and type of neoadjuvant therapy. Adjusted odds ratios (OR) and 95% confidence intervals (95%CI) were calculated. Type-I error rate was set to 5%. Statistical analyses were performed with SAS v9.3. Results: Out of 1,056 patients treated with neoadjuvant therapy for T3/T4 breast cancer, 107 (10%) had BCS and 949 (90%) had mastectomy. After adjusting for the aforementioned characteristics, Hispanic patients were more likely to have mastectomy (OR=3.50; 95%CI:1.38-8.84; p=0.008) than BCS. Compared to localized SEER stage, regional stage with direct extension (OR=3.24; 95%CI:1.60-6.54; p=0.001), regional direct extension and nodes (OR=4.35; 95%CI:1.72-11.03; p=0.002) and distant stage (OR=4.44; 95%CI:1.81-10.88; p=0.001) were significantly more likely to have mastectomy than BCS. Patients who received hormonal neoadjuvant therapy only (OR=0.29; 95%CI:0.12-0.68; p=0.004) were less likely to undergo mastectomy compared to patients receiving both chemo/hormonal therapy. Conclusions: Our study suggests that Hispanic ethnicity, advanced SEER stage, and type of neoadjuvant therapy are significant predictors of mastectomy after neoadjuvant therapy.