Background: Patients (pts) withborderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) are at high risk of margin positive resection with upfront surgery. Pre-operative stereotactic body radiation therapy (SBRT) may help sterilize vascular margins, but its additive benefit beyond multi-agent chemotherapy (CTX) is unclear. We report on long-term outcomes from a high-volume institution of BRPC/LAPC pts who were reviewed by a multidisciplinary team and explored after either multi-agent CTX alone or multi-agent CTX followed by SBRT. Methods: Consecutive BRPC/LAPC pts diagnosed 2011-2016 who underwent resection following CTX alone or CTX followed by 5-fraction SBRT (CTX-SBRT) were retrospectively reviewed. Baseline demographic, clinical, and treatment factors were compared between cohorts, and survival analysis was conducted to compare pathologic and survival outcomes. Results: Of 199 pts, 77 received CTX alone and 122 received CTX-SBRT. There was no significant difference between cohorts in age, gender, performance status, tumor location, CA19-9 at diagnosis, or post-CTX CA19-9 values (all p> 0.05). The CTX-SBRT cohort had a higher proportion of pts with LAPC as compared to the CTX cohort (53% vs 22%, p< 0.001). Modified FOLFIRINOX (mFFX) was administered to 55% of pts, while 70% of pts received either mFFX or gemcitabine/abraxane, with no difference between cohorts. Duration of CTX was longer in the CTX-SBRT cohort as compared to the CTX cohort (median 4.6 vs. 2.9 mos, p= 0.03), but adjuvant CTX was not given as often in the CTX-SBRT arm (60.4% vs. 86.4%, p= < 0.001). Notably, 30% of the CTX cohort also received adjuvant chemoradiation. Pathologic response was significantly improved in the CTX-SBRT cohort vs the CTX cohort, specifically negative margins (92% vs 70%, p< 0.001), node negative (59% vs. 42%, p< 0.001), and pathologic complete response (7% vs. 0%, p= 0.02). On multivariable analysis, after controlling for prognostic factors, CTX-SBRT remained significantly associated with margin negative resection (p< 0.001). Despite having more advanced stage and less adjuvant therapy administration in the CTX-SBRT cohort, there was no significant difference in overall survival after surgery (median OS: 24.6 vs. 22.2 mo, p= 0.79), local progression free survival (14.0 vs. 13.6 mo, p= 0.33), or distant metastasis free survival (16.4 vs. 11.8 mo, p= 0.33). Conclusions: Despite more advanced disease at presentation, BRPC/LAPC pts treated with CTX-SBRT were more likely to undergo margin negative resection and experienced similar survival outcomes, as compared to CTX alone. More data are needed to refine which patients benefit from neoadjuvant SBRT and how RT administration can be optimized to impact survival outcomes.