Background: The anti-HER2 antibody trastuzumab has vastly improved outcomes for women with early stage and advanced HER2+ breast cancer (BC) when used in combination with chemotherapy. Anthracycline and taxane-based regimens have historically made up the chemotherapy backbone for patients with localized HER2+ BC, though recent evidence suggests anthracyclines can be safely omitted. The single arm phase II APT trial established trastuzumab and paclitaxel as the standard adjuvant regimen for small HER2+ tumors. However, paclitaxel requires weekly treatment, causes alopecia, and has high rates of neuropathy and hypersensitivity reactions. In patients with metastatic HER2+ BC, the combination of trastuzumab and vinorelbine (TV) is effective and well tolerated. There is a need for alternative regimens for patients with HER2+ early-stage BC, especially for those with contraindications to anthracycline and taxane-based regimens. We conducted a retrospective study of patients with early stage HER2+ BC treated with adjuvant TV to evaluate a non-anthracycline/taxane-based, alopecia-sparing regimen. Methods: Clinicopathological characteristics, treatment details, and outcomes of patients with localized HER2+ BC treated with adjuvant TV for from 2007 to 2021 at a large academic medical institution were collected. Study endpoints included invasive disease-free survival (IDFS), overall survival (OS), and safety/tolerability. IDFS and OS were measured from start date of TV treatment to date of event or last follow-up, respectively. 5-year survival rates were generated in GraphPad Prism. Results: A total of 25 patients were treated with TV. All patients received trastuzumab at standard dosing and vinorelbine at a starting dose of 25 mg/m2 on days 1/8 of a 21-day cycle with 4 planned cycles. Median age at diagnosis was 61 years (range: 36-81). 88% of patients had anatomic pathologic Stage IA BC and 12% Stage IIA BC. Of the 25 patients, 24 of them opted to pursue TV due to concerns over alopecia, neuropathy, and other toxicities while 1 patient had received prior adriamycin and therefore opted for TV. With a median follow-up time of 68 months (5.7 years), the 5-year rate of survival from invasive disease was 90.9%, with 1 local and 1 distant recurrence. The 5-year overall survival was 100%. 76% of patients completed 4 cycles of TV without dose holds or delays and 92% completed 4 cycles without dose reductions. 2 patients required hospitalization during treatment with TV due to toxicity (diarrhea attributed to V, rigors/fever attributed to T). No patients experienced alopecia or long-term neuropathy. Conclusions: Trastuzumab in combination with vinorelbine in the adjuvant, early-stage setting for HER2+ BC is effective and well-tolerated and warrants further exploration as an alternative to taxane-based regimen.