Abstract Introduction: Traditionally, the venous drainage of pancreatic allografts is to the iliac vein. Recently, drainage via the portal system has become increasingly popular, as this route is thought to result in reduced hyperinsulinemia and therefore be more physiologic.. Herein, we describe our institutional experience with systemic versus portal drainage. Methods: Data was collected from 36 consecutive pancreas transplant patients. Results, expressed as mean ± SEM, were analyzed by the unpaired t-test. Graft and patient survival underwent Kaplan-Meier analysis and Logrank testing. Results: During the study period, 29 pancreas recipients had systemic drainage while 7 had portal drainage. Anastomic time was 40.6 ± 3.4 minutes in the portal group and 40.9 ± 2.5 in the systemic group (p = NS). Five patients with systemic drainage had splenic thromboses, while none were seen in those with portal drainage. There were no significant differences in hospital length-of-stay. Glucose levels and HgbA1c levels were not significantly different (Figure). Interestingly, C-peptide levels were similar throughout the first postoperative week. Patient and graft survival were similar. Each group had one patient with acute cellular rejection. Conclusions: Venous drainage via the portal system has similar outcomes to systemic drainage. Since we anticipated enhanced first-pass hepatic clearance in the portal drained group, it was surprising that C-peptide levels were similar between the two groups.