Background Locally advanced pancreatic cancer (LAPC) is associated with poor outcome, and clinical trials are imperative to address this. However, barriers to trial enrollment often exist, particularly in socio-economically challenged populations. Objective To evaluate the outcome of socio-economically challenged patients who had LAPC, multiple comorbidities, and who were not enrolled on clinical trials, but who were treated with the best standard-of-care. Methods We retrospectively reviewed the charts of 32 patients diagnosed as having LAPC who were referred to an urban cancer center between 2005 and 2010, analyzing the treatment and outcomes of 19 who underwent treatment at our center. Results In all 26.3% of the analyzed patients had commercial insurance, 31.6% did not identify English as their preferred language, and 84.2% had ≥ 3 comorbidities. The median overall survival was 19.1 months, with estimated 1- and 2-year survivals of 60.8% and 36.5%, respectively. The median survival for patients receiving chemotherapy followed by chemoradiation was 26.6 months. Toxicities were controllable. Translation services were required by 26% and social services interventions by 84%. Survival analysis based on insurance coverage did not show a significant association with levels of reimbursement. Limitations Retrospective study, small sample size, differences in chemotherapy types. Conclusions These patients, representative of a diverse and socio-economically challenged community, were able to receive standard-of-care therapies with acceptable toxicity and to achieve survivals comparable with clinical trials. This was achieved with intense supportive services.