Background: To assess outcomes of ER-negative breast CA pts treated with APBI, a matched-pair analysis was performed to determine efficacy of APBI vs whole breast RT (WBRT) from a single institution. Methods: From over 1650 pts treated with BCT from 1980-2013, a cohort of ER[-] pts treated with APBI or WBRT were investigated. Matched-pair analysis with a 1:1 ratio paired 79 APBI with 79 WBRT pts, all ER[-] (total:158). Match criteria included follow-up (FU) > 1.0 yr, stage, & age +/- 5 yrs. Outcomes analyzed included local recurrence (LR), true recurrence/marginal miss (TRMM), regional recurrence (RR), distant metastases (DM), disease-free (DFS), cause-specific (CSS), and overall survivals (OS). Results: As for clinical-pathological traits, no significant differences were noted for age (p=0.302), T-stage (p=1.000), tumor size (p=0.721), N-stage (p=0.062), use of chemoRx (p=0.747), endocrine Rx(p=0.408) or Herceptin (p=1.00). Per ASTRO Guidelines, no differences were seen in cautionary or unsuitable [UnS] groups between APBI & WBRT (p=0.333). With a mean FU of 8.0 yrs (10.1 yrs APBI; 8.4 yrs WBRT p<0.001), no differences were seen in the 10-yr actuarial rates of LR (9.3% vs 22.1% p=0.094), RR (1.3% vs 8.1% p=0.299), DM (7.1% vs 13.0% p=0.429), DFS (83.9% vs. 72.5% p=0.214), CSS (93.5% vs. 89.0 % p=0.677), or OS (79.6% vs. 80.1% p=0.573) between APBI & WBRT. Only TRMM was significantly different (0% APBI vs 12.5% p=0.011). In stratifying patients based on ER% (0%, 1-3%, 4-8%) no outcome differences were noted. Of the 158 ER[-] pts, 124 were cautionary with similar 10-yr outcomes except for TRMM (0% APBI;WBRT 14.4% p=0.017) & CLBF (0% APBI;WBRT17.1% p=0.019). For the 34 UnS patients, no endpoint differences were seen APBI vs WBRT. But, when the entire 158 ER[-] patients were analyzed for # of UnS factors, increasing UnS factors led to significant risk of RR (p<0.001) & DM (p=0.002). Conclusions: With 10-year FU of APBI for ER[-], the clinical results were equivalent to WBRT. No differences were noted based on ER%. Increasing number of unsuitable factors had more RR and DM. Maturation of randomized trial data will be needed to provide Class I evidence for equivalence of APBI to WBRT in ER[-] patients.