Tumor response and patterns of failure following intraoperative radiotherapy (IORT) of 42 patients with unresectable pancreatic cancers were evaluated by computed tomography (CT). At the time of maximum tumor regression, the tumor response rate following IORT was 52%, with three tumors showing CR. The median time of maximum tumor regression was 3 months after IORT. When tumor response was evaluated within 2 months of IORT, no significant difference in survival rate between responders and non-responders was noted. However, when tumor response was evaluated 3-6 months after IORT, the responders showed a significantly better survival rate than the non-responders. Local tumor recurrence, liver metastasis, and peritoneal dissemination were major causes of failure after IORT for unresectable pancreatic cancers. In addition, the median time of detection of these findings by CT was 2-3 months after IORT. Thus, our results indicate that CT performed 3-4 months after IORT is most important for predicting clinical outcome.