Aim: This study aimed to investigate the effect of pancreatic ductal adenocarcinoma (PDAC) on the alterations in red blood cell aggregation related to angiogenesis and hypoxia markers. Material and Methods: We studied 32 patients with confirmed PDAC. The aggregation of red blood cells (RBCs) were evaluated using a Laser-assisted Optical Rotational Cell Analyzer (LORCA). Serum vascular endothelial gfowth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α) levels were measured by an ELISA method. The following parameters specific to the aggregation process were estimated: the aggregation index (AI), the aggregation half-time (t1/2), and the threshold shear rate (γthr). Results: All measured RBC aggregation parameters among PDAC subjects differed from those in controls. The AI (P<0.05) and γthr (P<0.005) were significantly higher in the PDAC group, whereas t1/2 (P<0.01) and AMP (P<0.001) were significantly lower compared to the control group. The levels of VEGF (p<0.0001) and HIF-1α (p<0.0001) were significantly higher in the PDAC group than in the control group. There were significant correlations between RBC aggregation parameters and VEGF and HIF-1α. Conclusion: For the first time, we have demonstrated RBC aggregation disturbances in patients with pancreatic carcinoma. We also found that circulating levels of angiogenesis and hypoxia biomarkers are significantly elevated compared to the control group. Further studies are needed to explore the pathophysiological mechanisms linking PDAC to these aggregation indices.