Despite recent progress with novel chemotherapy regimens, pancreatic ductal adenocarcinoma remains the fourth leading cause of cancer death in the United States. Innovative approaches to treatment of this disease are needed to accelerate progress. A review was conducted of the results of 2 pancreatic cancer vaccine programs with results that have shown promise in early-phase clinical trials. In a phase 2 trial, a cell-based allogeneic pancreatic cancer vaccine exploiting the hyperacute rejection response targeted against alpha-1,3 galactosyl epitopes (algenpantucel-L) has shown improvement in disease-free and overall survival rates in the adjuvant setting compared with a historical control. This vaccine has advanced to ongoing phase 3 trials. Compared with GVAX alone, a second whole-cell vaccine employing GM-CSF-expressing pancreatic cancer cells (GVAX) to enhance the antigen presentation in a priming phase followed by a Listeria-based vaccine targeting mesothelin in a boost phase improved survival rates. This vaccine platform is undergoing additional phase 2 testing. Allogenic whole-cell pancreatic adenocarcinoma vaccines show promise in early-phase trials and have the potential to improve survival rates by unleashing antitumor immunity.