Background: The optimal neoadjuvant treatment for HER2-positive breast cancer is unknown. We wanted to compare the efficacy and safety of the anthracycline regimen EC-TH versus nonanthracycline regimen TCH in neoadjuvant setting for HER2-positive breast cancer. Methods: Patients with stage II or III HER2-positive breast cancer were randomly assigned to either four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel and trastuzumab (EC-TH) every 3 weeks during all chemotherapy cycles, or six cycles of docetaxel and carboplatin plus trastuzumab (TCH) every 3 weeks. The primary endpoint was pathological complete response (defined as the absence of invasive tumour cells in breast and axilla, ypT0/is ypN0). This trial is registered with ClinicalTrials.gov, number NCT03140553. Results: From September 2016 to November 2019, 140 patients were randomly assigned, and 131 were evaluable for the primary end-point. The pathological complete response was recorded in 25 (38.5%, 95% confidence interval [CI] 26.6–50.2) of 65 patients in the EC-TH group and in 37 (56.1%, 44.1–68.0) of 66 in the TCH group (p=0.044). In the EC-TH group, 15 (23.1%) of 65 patients underwent breast-conserving surgery. In the TCH group, 21 (31.8%) of 66 patients underwent breast-conserving surgery. There was no difference in the proportions of patients undergoing breast-conserving surgery between the two treatment groups (p=0·262). The most common adverse events were neutropenia (in 23 [35.4%] of 65 patients in the EC-TH group vs 27 [40.9%] of 66 in the TCH group), anemia(in 33 [50.8%] of 65 patients in the EC-TH group vs 34 [51.5%] of 66 in the TCH group) and thrombocytopenia (in 5 [7.7%] of 65 patient in the EC-TH group vs 17 [25.8%] of 66 in the TCH group). Conclusion: This is the first multicenter prospective randomised phase II trial compare EC-TH with TCH for neoadjuvant therapy in HER2-positive breast cancer. There was a similar incidence of AEs but a higher pCR rate in TCH arm compared with the EC-TH arm. TCH regimen might be a preferred approach in patients with HER2-positive breast cancer. Long-term follow-up is required to confirm these results. Clinical trial information: NCT03140553.