Neoadjuvant chemotherapy (NACT) has been widely used in breast cancer patients. The aim of the study was to compare survival outcomes between breast cancer patients receiving NACT, with and without complete pathologic response (pCR), and those receiving adjuvant chemotherapy (ACT).Based on the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 48,350 breast cancer patients, 15,525 of whom with pCR after NACT, and 124,202 patients after ACT during the period of 2010-2021. In comparison with patients in ACT group, we assessed hazard ratios (HRs) of breast cancer-specific and overall mortality among individuals in NACT using Cox regression.During the period of follow-up (median 5 years), 4,800 and 8,257 breast cancer-related deaths were identified among patients in NACT and ACT group, respectively. Patients in NACT group had unfavorable molecular type (human epidermal growth factor receptor 2 overexpression, triple negative), more advanced tumor features (higher grade and stage) and was more likely to undergo mastectomy and radiotherapy. Moreover, patients undergoing NACT had higher cumulative mortality rate of breast cancer (19.60% vs 10.46%), compared with those receiving ACT. After controlling for covariates, NACT patients were at increased risk of breast cancer-specific mortality (HR 1.47, 95% CI 1.41-1.53) compared with ACT patients. In contrast, NACT patients with pCR were associated with an improved breast cancer-specific survival (HR 0.59, 95% CI 0.54-0.64). The elevated risk was obviously greater among NACT patients in NACT-disfavored subgroups including lobular/mixed histology, well/moderately differentiated grade, local cancer stage, or HR+/HER2- molecular subtype (HRs 1.63-1.93).NACT patients have worse survival, compared with their ACT counterparts. Although patients with pCR after NACT derive significant survival benefits, NACT-disfavored subgroups may gain limited benefit from NACT, and alternative approaches should be considered.© The Author(s) 2025. Published by Oxford University Press.