This study aimed to evaluate venous hemodynamic and morphological changes and associated factors in patients with Peripherally Inserted Central Catheters (PICCs), to provide evidence for rational clinical use of PICCs. Venography was performed at different time points in 87 patients with PICCs to observe hemodynamic, morphological, and structural changes. Related laboratory blood tests were also performed. Venous hemodynamic changes and structural abnormalities were observed in 77 patients following PICC placement, and blood tests showed significant changes. The effects of a PICC on hemodynamic and morphological changes are closely related to vein diameter, prothrombin time, fibrinogen level, and hemorheological parameters. Selection of larger peripheral veins and the use of measures that can modify hemorheological parameters, reduce fibrinogen level, and prolong the prothrombin time can reduce the incidence of PICC-related complications.