Some patients with gastroparesis (GP) require sustained central intravenous access for hydration, medication and/or nutrition, leaving them at risk for venous thrombosis. We studied a group of 53 patients with gastroparesis for identifiable risk factors of clinically significant thrombosis. Patients requiring prolonged central IV access fell into two groups: those who had clinical incidence of IV catheter-related thrombosis confirmed radiologically (CLOT, n = 14), and those who did not form IV catheter thrombosis (NOCLOT, n = 39). We analyzed and compared clinical symptoms, serum/plasma coagulation studies, and autoimmune antibodies in the CLOT and NOCLOT groups. Patients in the CLOT group had statistically more Scl 70 antibodies than did the NOCLOT group, and another autoantibody, Ku 66, was found in higher titers in the NOCLOT group than the CLOT group. Other autoimmune and coagulation factors were not statistically different between the two groups, although a subgroup of CLOT patients had lower plasma Protein S levels. We conclude that the presence of Scl 70 autoantibodies is associated with increased clotting risk in this group of GP patients, and that the Ku 66 antibody may be associated with decreased risk of thrombosis in patients with GP. These findings, coupled with lower Protein S levels in some CLOT patients, suggests that autoimmune factors may be associated with GP patients who thrombose IV access versus patients who do not.