Background: The role of conventionally fractionated radiation therapy in the management of locally advanced pancreatic cancer (LAPC) is controversial. One concern about concurrent chemoradiation relates to the timing of systemic chemotherapy. In contrast to conventional radiation therapy, SBRT delivers high doses in a shorter duration resulting in minimal disruption in chemotherapy. Here we report our results of patients treated with SBRT and chemotherapy for LAPC. Methods: Twenty-seven patients treated with SBRT for LAPC at our institution from January 1, 2008 to December 31, 2012 were included in this retrospective analysis. Treatment was delivered in 5 fractions of 5 or 6 Gy per fraction in one week. The PTV included the pancreatic mass plus adjacent vasculature in most patients. The majority of patients received concurrent chemotherapy. Median time from diagnosis to SBRT was 1.9 months. Toxicities were scored using the CTCAE v.3. Survival was calculated using the Kaplan-Meier method. Results: The median age was 63 (range 45 – 90). ECOG performance status ranged from 0 – 2 and median Charlson Comorbidity Index was 3, range 0 – 7. All patients completed radiation as prescribed except one, who is excluded from survival analysis. Twenty-five patients received concurrent chemotherapy: 18 received gemcitabine, 6 received mFOLFOX and 1 received capecitabine. Two other patients received sequential chemotherapy. At the time of this analysis, 25 patients had died and the median OS from diagnosis was 13 months. Median PFS was 8.7 months. The first site of radiographic failure was local in 2 patients, local and distant in 1, and distant in 17. Of the other 7 patients, most died after clinical deterioration with no evidence of progression at last imaging. Acute toxicity was minimal. Severe late SBRT-related toxicities included one grade 4 biliary stricture and a grade 5 gastric hemorrhage without prior radiographic tumor progression. Conclusions: SBRT combined with gemcitabine or 5-FU based chemotherapy for LAPC is convenient, feasible and generally well tolerated. The outcomes of SBRT combined with chemotherapy compare favorably to the results of treatment with chemotherapy and conventional RT.