The liver is the preferred site for islet transplantation (ITx) but not ideal due to limitations affecting engraftment. We evaluated the safety and efficacy of ITx in the omentum using a resorbable biological scaffold in 3 subjects with type 1 diabetes and negative C-peptide. Islets were combined with autologous plasma and thrombin to generate a biologic scaffold and layered laparoscopically on the omentum. Induction was with anti-thymocyte globulin and etanercept. Maintenance was with mycophenolate sodium and tacrolimus. Demographics, islet dose and metabolic data are shown in the Table.Subject #Age (years)Duration T1DM (years)BMI (Kg/m2)IEQ†/KgMMTT‡ Stimulated Glucose (mg/dl)/C-peptide (ng/ml)Insulin dose U/Kg/day (Units/day)HbA1c%6 months12 months24 monthsPre-ITxLatestPre-ITxLatest1432621.511,386181/3.32277/1.79317/0.490.62 (33)0.14 (7)6.85.32321625.39,635372/0.88374/0.65332/0.52*0.45 (31)0.45 (30)5.75.6346422412,648277/2.47--0.45 (20)0.2 (11)6.36.3* 18 months Post-ITx † IEQ= islet equivalents ‡ MMTT = mixed meal tolerance test Subject 1 was insulin independent for 15 months and maintains stable glycemic control. Subject 2 had marginal graft function with persistence of severe hypoglycemia (SH) and then underwent intrahepatic ITx resulting in insulin independence. Subject 3 had a 55% reduction in insulin dose and maintains excellent glycemic control. Our initial experience demonstrates feasibility and safety of ITx on the omentum. Graft function persisted throughout follow-up (6-24 months) resulting in improved glycemic control and absence of SH (subjects 1 and 3). Results suggest a significant loss of islets early post-ITx followed by gradual functional decline similar to intrahepatic ITx. Strategies to improve oxygen delivery and neo-vascularization and minimize immunosuppression are needed to improve long-term outcomes at this site. Disclosure D. Baidal: None. C. Ricordi: None. D.M. Berman: Stock/Shareholder; Self; Pfizer Inc. A. Pileggi: Stock/Shareholder; Self; Converge Biotech, Inc.. Stock/Shareholder; Spouse/Partner; Converge Biotech, Inc. A.M. Alvarez Gil: None. N. Padilla: None. G. Ciancio: None. E. Linetsky: None. R. Alejandro: None.