Total pancreatectomy with islet autotransplantation (TPIAT) is performed to relieve pain and allow for a better quality of life for patients with the most severe and disabling manifestations of recurrent acute and chronic pancreatitis. Several large centers have now reported data on outcomes at 5–10 years after TPIAT. In the largest series, long-term survival is 85% at 10 years after TPIAT. Opioid use decreases over time, with approximately 70% of individuals off opioids at 10 years after surgery and over 80% of individuals reporting pain reduction and robust improvements in quality of life that are sustained over time. Pain relief and opioid discontinuation are greatest in the youngest patients (children) and oldest patients (>50 years). A successful IAT procedure results in higher quality of life and reduced diabetes distress than TP alone. In the first 5 years after TPIAT, most patients have islet graft function, with 20–30% of patients completely off insulin, and even 10 years after TPIAT, more than 10% of patients remain off insulin. Young children have higher rates of insulin independence and better sustained islet function. Those individuals receiving >5000 islet equivalents per kilogram of body weight have better islet function and glycemic control and are more likely to be off insulin through 10 years of follow-up than those with a lower islet mass transplanted.