Over 1 million people with diabetes use insulin pumps and insert a new continuous subcutaneous insulin infusion (CSII) set every 2-3 days for adequate blood glucose control. Insulin absorption from the subcutaneous tissue is slow and varies over time. This can lead to complications such as hypoglycemia and diabetic ketoacidosis. Furthermore, the repeated trauma of insertion contributes to scar tissue formation and may result in infusion site loss. The development of an extended-wear CSII infusion set that can improve the safety and efficacy of CSII therapy would be a major advantage and facilitate proper glycemic control for diabetic patients. A prototype infusion set was developed using a soft polymer material with multiple ports and tested against commercially available single-port infusion sets in ambulatory large swine. Infusion sets were inserted into the subcutaneous tissue every other day for 8 days. A 70µL bolus of insulin and contrast agent was infused through each cannula 5 minutes prior to excision, then specimens were frozen and Micro-CT imaged. The 3D distribution and surface area of contrast agent in contact with adjacent vascular tissue were evaluated. We hypothesized that multiple-ports would increase fluid dispersion, allowing the insulin to reach more functional capillary and lymph vessels. Investigational sets had a statistically significant larger surface area (p=0.005) and volume (p=0.001) of contrast agent spread when compared with commercial infusion sets, potentially supporting our objective of reaching more vessels to achieve consistent insulin absorption over time. Results from this research have guided the design and development of a next-generation infusion set. Clinical translation of this investigational design could result in a reliable insulin delivery system that simplifies diabetes management, improves quality of life, and benefits clinical outcomes. Disclosure D. Diaz: None. A.R. Dinesen: None. A. Khalf: None. G.J. Eisler: None. C. Loeum: None. M.C. Torjman: Advisory Panel; Self; Capillary Biomedical, Inc. P.J. Strasma: Board Member; Self; Capillary Biomedical, Inc.. Stock/Shareholder; Self; Capillary Biomedical, Inc.. Employee; Self; Capillary Biomedical, Inc. J.I. Joseph: Stock/Shareholder; Self; Capillary Biomedical, Inc.. Advisory Panel; Self; Capillary Biomedical, Inc.. Research Support; Self; Capillary Biomedical, Inc.. Stock/Shareholder; Spouse/Partner; Capillary Biomedical, Inc.. Advisory Panel; Self; Thermalin Diabetes, LLC.. Research Support; Self; Thermalin Diabetes, LLC.. Advisory Panel; Self; Thermalin Diabetes, LLC.. Stock/Shareholder; Self; Thermalin Diabetes, LLC.. Research Support; Self; National Institutes of Health, JDRF. Speaker's Bureau; Self; Capillary Biomedical, Inc..