Abstract Background While [18F]fluoromisonidazole (FMISO), a representative PET tracer to detect hypoxia, is reported to be able to prospect the prognosis after treatment for various types of cancers, the relation is unclear for pancreatic cancer. The aim of this study is to assess the feasibility of [18F]FMISO PET/CT as a preoperative prognostic factor in patients with pancreatic cancer. Methods Patients with pancreatic cancer who had been initially planned for surgery received [18F]FMISO PET/CT. Peak standardized uptake value (SUV) of the pancreatic tumor was divided by SUVpeak of the aorta, and tumor blood ratio using SUVpeak (TBRpeak) was calculated. After preoperative examination, surgeons finally decided the operability of the patients. TBRpeak was compared with hypoxia-inducible factor (HIF)-1α immunohistochemistry when the tissues were available. Furthermore, correlation of TBRpeak with the recurrence-free survival and the overall survival were evaluated by Kaplan-Meyer methods. Results We analyzed 25 patients with pancreatic adenocarcinoma (11 women and 14 men, median age, 73 years; range, 58–81 years), and observed for 39–1101 days (median, 369 days). Nine cases (36.0%) were identified as visually positive of pancreatic cancer on [18F]FMISO PET/CT images. TBRpeak of the negative cases was significantly lower than that of the positive cases (median 1.08, interquartile range (IQR) 1.02–1.15 vs median 1.50, IQR 1.25–1.73, p  1000 days, p = 0.04). Conclusions [18F]FMISO PET/CT has the possibility to be a preoperative prognostic factor in patients with pancreatic cancer.