Purpose: The delivery of high-quality radiation therapy to pancreatic adenocarcinoma requires accurate localization. Radiopaque implanted fiducial markers (IFM) and self-expandable metallic stents (SEMS) have both been proposed as means of achieving accurate localization in image guided radiation therapy (IGRT). The suitability of IFM and SEMS for localization were evaluated in this study based on geometric and dosimetric surrogates. Methods and materials: In a retrospective study of 54 patients with pancreatic cancer who underwent tumor-directed IGRT, 9 were identified as having both IFM and SEMS. For each patient, cone beam computed tomography (CT) scans from each of 6 weeks of treatment were selected for review and comparison with the simulation CT. The centroids of both the IFM and SEMS on each cone beam CT were aligned with those on the planning CT to quantify geometric differences between IFM- and SEMS-based localization. This difference was used to mark the isocenter displacement from the original IFM-localized treatment plan to evaluate the dosimetric implications of SEMS localization. IFM were used as the localization standard given their intratumoral location, and the stability of IFM was evaluated by variability of intrafiducial distance. The original treatment plan was computed on the planning CT at the isocenter shifted by the determined displacement, and dose-volume histograms were calculated for the target volume and organs at risk. Results: The average displacement for SEMS localization over all fractions in all patients was 7.7 mm. Planning target volume coverage by 90% of prescription dose was significantly reduced (mean, 11.1%; range, 0.5% to -46.6%) for SEMS compared with IFM localization (P <.05). Dose tolerances were exceeded for stomach, duodenum, and small bowel for 3, 3, and 5 of 9 patients, respectively, when SEMS localization was used. Conclusions: SEMS-based compared with IFM-based localization results in significant variability of radiation therapy localization for pancreatic cancer. IFM-based localization should be considered the standard of care for tumor-directed pancreatic cancer IGRT.