Background: Distant recurrence (DR) is the cause of most breast cancer deaths. The 21-gene assay (ODX) Recurrence Score (RS) result predicts both 5 and 10-yr DR risk and can guide adjuvant chemotherapy (CT) recommendations to mitigate this risk. This study analyzed the use of the RS result to guide adjuvant treatment decisions in a large single-institution, prospective cohort of patients (pts). Methods: This is an IRB-approved review of a prospective database of pts receiving ODX on an initial primary breast cancer. Data collected included demographics, primary operation, margin status, receptor status, RS, adjuvant treatment, recurrence, and survival. Pts were stratified as low risk (RS < 18), intermediate risk, or high risk (RS > 30). The primary analysis computed Kaplan-Meier estimates for rate of DR at 5 yrs when pts were stratified by RS. Results: From 2003 to 2009, a RS result was obtained on 606 pts. Median follow up was 2.9 yrs (0.1-9.7) and median age was 58 yrs (27-84). Median RS result was 16 (0-63); 344(57%) pts were low, 212(35%) intermediate, 50(8%) high. Endocrine therapy was given to 92.4%, 94.3%, and 87.5% low, intermediate, and high risk pts, respectively. Adjuvant CT was given to 8.6%, 47.6%, and 70.8% low, intermediate, and high risk pts, respectively. There were 8 DR events with 1.8% 5-yr estimated risk of DR. The 5-yr estimated risk of DR was 0.7% for low risk (344) pts, 3.4% for intermediate risk (211) pts, and 2.6% for high risk (50) pts. Among node negative [N(-)] pts (502), the 5-yr estimated risk of DR was 0.8% for low risk (287) pts, 3.7% for intermediate risk (174) pts, and 3.3% for high risk (41) pts. Among node positive [(N+)] pts (54) there was only 1 DR, which was in a high risk pt. Of pts with unknown nodal status (50), there were no DRs. Conclusions: The RS result is predictive of DR at 5 yrs as shown in historical datasets (Table). The use of ODX to guide adjuvant treatment recommendations in our contemporary, prospective cohort resulted in a much lower 5-year DR rate and thus supports its use to guide adjuvant treatment decisions.