© 2017 Saudi Journal of Gastroenterology.Background/Aims: To evaluate the prognostic significance of plasma caveolin (CAV)-1 and its association with survival and treatment response rates in metastatic pancreatic cancer (MPC). Patients and Methods: Plasma samples were prospectively collected from 41 patients with newly diagnosed MPC. Moreover, plasma samples were collected from 48 patients with chronic pancreatitis and 41 healthy individuals (control groups) for assessing Cav-1 levels. Plasma Cav-1 levels were evaluated at baseline and after three cycles of chemotherapy in the patients with MPC. Results: The median Cav-1 level was 13.8 ng/mL for the patients with MPC and 12.2 ng/mL for healthy individuals (P = 0.009). The Cav-1 cut-off level was calculated as 11.6 ng/mL by using the receiver operating characteristic curve. The median overall survival and progression-free survival rates were 5 and 2.4 months, respectively, for participants with a high basal plasma Cav-1 level; the corresponding values were 10.5 and 9.4 months for participants with a low plasma Cav-1 level (P = 0.011 and P= 0.003, respectively). Of the 41 patients with MPC, 23 completed at least three cycles of chemotherapy. The median Cav-1 level was 13 ng/mL for post-treatment MPC (r2: 0.917; P= 0.001). High basal plasma caveolin-1 level have continued to remain at high levels even after chemotherapy, showing a trend toward worse response rates (P = 0.086). Conclusion: High basal plasma Cav-1 levels seem to be associated with poor survival and tend to yield worse therapeutic outcomes in patients with MPC. This study is the first to evaluate the prognostic significance of plasma Cav-1 levels as a prognostic factor in patients with MPC. However, larger prospective clinical trials are warranted.