Background: Lymphovascular invasion (LVI) is considered a negative prognostic factor in early breast cancer, but its role in decision-making regarding adjuvant chemotherapy is unclear in the current era of molecular profiling. This study sought to evaluate the association of LVI status with the recurrence score (RS) on the multigene Oncotype DX (ODX) assay and its impact on outcome. Methods: Patients with early estrogen receptor-positive breast cancer who underwent ODX analysis in 2005–2012 were retrospectively identified. Clinical data were collected from the medical records. The Cox proportional-hazards ratio was used to determine recurrence rates. The prognostic significance of LVI was evaluated by competing risks analysis. Results: LVI was detected in 38 of 657 patients (6%). LVI was not associated with ODX RS (p = 0.225). However, it was significantly associated with other known prognostic factors and with worse 5-year disease-free survival (HR 2.93; 95% CI 1.02–8.39; p = 0.04). Overall survival (OS) analysis according to the ODX subgroups showed that the presence of LVI was associated with worse 5-year OS (p = 0.04) only in the intermediate-risk group, while LVI had no effect on the low- or high-risk groups. Conclusions: Although LVI was not significantly associated with a higher ODX RS, it may infer a worse outcome, especially in ODX intermediate-risk patients.