Patients with heterotaxy syndrome (HS) can present with an associated complete dorsal pancreas agenesis (DPA). They are considered to be at increased risk for developing diabetes due to a reduced functional beta cell mass (FBM) as well as for chronic pancreatitis leading to unmanageable pain. We report the case of a young female with chronic pancreatitis due to HS and associated DPA. She presented with a severe persisting upper abdominal pain refractory to non-surgical treatment. Unlike in previously reported cases, she had a high FBM (i.e. 150% of normoglycemic controls) as determined by hyperglycemic clamp. She underwent a total pancreatectomy followed within 24 hours by an intraportal autologous islet cell transplant containing 4 x 106 beta cells (4,700 IEQ)/kg bodyweight. After surgery, the pain resolved, eliminating the need for analgesics. The intraportal implant established an adequate FBM (72% of controls at posttransplant month 2) achieving glycemic control without need for insulin administration. A hyperglycemic clamp can assess utility and efficacy of an intraportal islet cell autotransplant following total pancreatectomy in patients with HS and complete DPA.