287 Background: To retrospectively compare the efficacy and toxicity of full-dose gemcitabine-based chemoradiotherapy (GemRT) vs. 5-fluorouracil (5-FU)-based chemoradiotherapy (5FURT) for locally advanced pancreas cancer (LAPC). Methods: From January 1998 to December 2008, 93 patients with LAPC were treated either with 5FURT (n=38) or GemRT (n=55). 5FURT consisted of standard-field radiotherapy given concurrently with infusional 5-FU or capecitabine. GemRT consisted of involved-field radiotherapy given concurrently with full-dose gemcitabine (1000 mg/m2 weekly) with or without erlotinib. The follow-up time was calculated from the time of diagnosis to the date of death or last contact. Results: Eighty-eight of 93 patients have died, and only one was lost to follow-up after developing DM. The median OS was 11.2 months (range 1.5-96). Patient characteristics (including Zubrod score, age, tumor stage, nodal stage, tumor location, and grade) were not significantly different between treatment groups. The OS was significantly better for GemRT compared to 5FURT (median 12.5 months vs. 10.2 months; 51% vs. 34% at 1 year; 12% vs. 0% at 3 years; 7% vs. 0% at 5 years; respectively; p=0.04), although the two groups had same DM (34% at 1 year). GemRT cohort was more likely to receive gemcitabine before or after chemoradiotherapy than 5FURT cohort (85% vs. 37%, p<0.001). Of the subset who received gemcitabine either before or after chemoradiotherapy, OS was still significantly better for GemRT without concurrent erlotinib compared to 5FURT (median 15.1 months vs. 10.7 months; 70% vs. 36% at 1 year; 21% vs. 0% at 3 years; 11% vs. 0% at 5 years; respectively; p=0.005), as was the rate of DM (23% vs. 45%; respectively; p=0.04). The subsequent hospitalization, percent of survival time spend in the hospital, acute and late grade 3-5 gastrointestinal toxicities were not significantly different between the GemRT and 5FURT groups. Conclusions: Full-dose GemRT was associated with improved OS compared to standard 5FURT. This approach yielded a moderate number of long-term survivors and was not associated with increased hospitalization or severe gastrointestinal toxicity. No significant financial relationships to disclose.