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Introduction: This study aimed to compare the efficacy and safety of docetaxel + trastuzumab + pertuzumab and docetaxel + carboplatin + trastuzumab + pertuzumab for treating HER2-positive breast cancer. Method: HER2-positive breast cancer from patients diagnosed between January 2020 and September 2022 were included in this retrospective study. Docetaxel + trastuzumab + pertuzumab or docetaxel + carboplatin + trastuzumab + pertuzumab was selected as the neoadjuvant regimen. The primary endpoint was a complete pathological remission rate. Secondary endpoints were toxicity during neoadjuvant treatment, adjustment of the neoadjuvant therapy scheme, and adjuvant medication. Result: A total of 81 patients were included in this study (38 in the docetaxel + carboplatin + trastuzumab + pertuzumab treatment group and 43 in the docetaxel + trastuzumab + pertuzumab group). The complete pathological remission rates in the docetaxel + carboplatin + trastuzumab + pertuzumab and docetaxel + trastuzumab + pertuzumab groups were 44.7% (95% confidence interval: 30.2%-60.3%) and 51.2% (95% confidence interval: 36.8%-65.4%), respectively. The incidence of grade 3 or higher toxicity in the docetaxel + carboplatin + trastuzumab + pertuzumab group was significantly higher than that in the docetaxel + trastuzumab + pertuzumab group (68.4% vs 39.5%, P  = .009). Neutropenia and asthenia were the most common grade 3 or higher toxicities. The incidence of neoadjuvant scheme adjustment was significantly higher in the docetaxel + carboplatin + trastuzumab + pertuzumab group than in the docetaxel + trastuzumab + pertuzumab group (26.3% vs 7.0%, P  = .039). The proportion of patients who received <6 cycles of neoadjuvant therapy was significantly higher in the docetaxel + carboplatin + trastuzumab + pertuzumab group than in the docetaxel + trastuzumab + pertuzumab group (31.6% vs 4.7%, P  = .004). Patients in the docetaxel + carboplatin + trastuzumab + pertuzumab group received higher doses of granulocyte-macrophage colony-stimulating factor. Conclusion: In the neoadjuvant treatment of HER2-positive breast cancer, the docetaxel + trastuzumab + pertuzumab regimen might be more tolerated than the docetaxel + carboplatin + trastuzumab + pertuzumab regimen and did not show a lower complete pathological remission rate. However, our findings require further validation through prospective studies.