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We reviewed the current state of total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis and recurrent acute pancreatitis (RAP).An increasing number of centers in the United States and internationally are performing TPIAT. In selected cases, TPIAT may be performed partially or entirely laparoscopically. Islet isolation is usually performed at the same center as the total pancreatectomy surgery, but new data suggest that diabetes outcomes may be nearly as good when a remote center is used for islet isolation. Ongoing clinical research is focused on patient and disease factors that predict success or failure to respond to TPIAT. Causes of persistent abdominal pain after TPIAT may include gastrointestinal dysmotility and central sensitization to pain. Several clinical trials are underway with anti-inflammatory or other islet protective strategies to better protect islets at the time of infusion and thereby improve the diabetes results of the procedure.In summary, there is an increasing body of literature emerging from multiple centers highlighting the benefits and persistent challenges of TPIAT for chronic pancreatitis and RAP. Ongoing study will be critical to optimizing the success of this procedure.