Background <p>The study investigates the prognostic differences between breast-conserving surgery (BCS) and mastectomy in patients with invasive ductal carcinoma of the breast who achieve a complete response (CR) after neoadjuvant chemotherapy.</p> Methods <p>This study analyzed data from 9,411 patients diagnosed with invasive ductal carcinoma of the breast who achieved complete response following neoadjuvant chemotherapy, using data from the SEER database between 2010 and 2019, comprising 4,219 patients in the BCS group and 5,192 in the mastectomy group. Propensity score matching (PSM) was employed to control for confounding variables, and univariate and multivariate analyses were performed to identify variables associated with overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier survival curves were used to evaluate the prognosis of patients in the two groups.</p> Results <p>The multivariate Cox regression analysis demonstrated that histological subtype, T stage, N stage, surgical method, and radiotherapy were risk factors for CSS, while age, histological subtype, T stage, and N stage were associated with OS (<i>p</i> &lt; 0.05). Following matching, the Kaplan-Meier survival analysis curve suggested that the BCS group had higher CSS than the mastectomy group (<i>p</i> &lt; 0.05), although there was no statistically significant difference in OS between the two groups (<i>p</i> = 0.16). Subgroup analysis revealed that, among patients aged ≤ 50, of White ethnicity, with grade 3 tumors, and HR+/HER-2- subtype, the BCS group exhibited superior CSS compared to the mastectomy group (<i>p</i> &lt; 0.05).</p> Conclusion <p>Patients with invasive ductal carcinoma of the breast who achieve complete response following neoadjuvant chemotherapy experience better CSS benefits with BCS compared to undergoing mastectomy.</p>