Objective To analyze the prognostic factors in the patients with HER2-positive breast cancer adjuvant treated with trastuzumab. Methods We conducted a retrospective analysis of clinical data of 1 246 patients diagnosed with HER2-positive breast cancer between January 2009 and December 2019 who received treatment with trastuzumab. We investigated the factors impacting their prognosis by the Log-rank test univariate analysis and multivariate COX regression analysis. Results HER2-positive patients treated with trastuzumab had a poor prognosis in pT_2-3(HR=2.10, P=0.003), pN_2-3(HR=2.81, P<0.001), and no endocrine therapy (HR=2.50, P<0.001), and that had a better prognosis combined with taxane or other chemotherapy regimens (HR=0.40, P=0.017). We divided the patients into two subgroups according to the status of lymph node metastasis, and we found that in the negative lymph nodes group the patients with pT_2-3 stage had poor prognosis (P=0.020), while the patients combined with taxane or other chemotherapy had better prognosis (P=0.032). In the positive lymph nodes group the patients with pT_2-3 stage and no endocrine therapy had poor prognosis (P=0.012, P=0.001). Conclusions The patients with HER2-positive breast cancer treated with trastuzumab can be managed in different categories, for individuals without lymph node involvement and small tumor sizes, combining therapy with non-anthracycline chemotherapy is preferable for achieving improved outcomes, for patients with lymph node metastasis and large tumor sizes, if chemotherapy options are available, it is more recommended to use an anthracycline-free regimen to ensure the same prognosis while reducing the harm caused by the toxic side effects of chemotherapy.