As of December 31, 2004, more than 23,000 pancreas transplant had been reported to the IPTR, >17,000 in the US and almost 6000 from outside the US. An analysis of US pancreas transplants performed between 1988 and 2003 showed a progressive improvement in outcome, with pancreas transplant graft survival rates (GSRs) going from 75% at 1 yr for 1988/1989 to 85% for 2002/2003 simultaneous pancreas-kidney (SPK) cases, from 55 to 78% for pancreas after kidney (PAK) cases, and from 45 to 77% for pancreas transplants alone (PTA) cases. The improvements were due both to decreases in technical failure (TF) rates (from 12 to 6% in SPK, 13-8% in PAK, and 24-7% in PTA) and immunological failure rates (going from 7 to 2% for SPK, from 28 to 7% for PAK, and from 38 to 8% for PTA cases). These results are even more impressive under the aspect that during the same time the rate of potential risk factors increased and the duct management techniques changed from bladder to enteric drainage. The improvement in outcome allowed also an increase in the number of solitary pancreas transplants from initially 12% to now 35%. Contemporary primary deceased donor pancreas transplant outcomes were calculated separately for 2000-2004 US and non-US cases. The US patient survival rates at 1 yr were >95% in each recipient category, with 1 yr primary pancreas GSRs of 85% for SPK, 78% for PAK, and 76% for PTA (p < 0.0001). The immunological graft failure rates for 2000-2004 technically successful (TS) SPK, PAK, and PTA cases were 2, 8, and 10% at 1 yr (p = 0.0001). In the majority of all transplants ED was used for duct management (81% of SPK, 67% of PAK, and 56% for PTA cases). Of the ED transplants, venous drainage via the portal system was used for 20% of SPK, 23% of PAK, and 35% of PTA cases. Duct management technique did not have a significant impact on overall pancreas graft function in the univariate or the multivariate model. The outcomes of ED and BD transplants are comparable with 85 vs. 87% at 1 yr for SPK, 77 vs. 80% for PAK, and 72 vs. 79% for PTA. The overall TF rate was higher in ED pancreas transplants but this difference did reach significance only in SPK. In addition, in technically successful PTA the immunological graft loss rate was higher in ED vs. BD transplants (15 vs. 5% at 1 yr). The different vascular management techniques did not seem to have an impact on the outcome of the pancreas transplants. Kidney GSRs were not significantly different for ED vs. BD SPK cases, 93 and 91% at 1 yr (p = 0.24). The overall conversion rate from BD to ED was 9% at 1 yr and 17% at 3 yr post-transplant. The most influential factor for patient survival in SPK and PAK in the multivariate and the univariate models was the status of the transplanted organ. The hazard ratio (HR) for a failed kidney was 14.99 in SPK and 9.17 in PAK (p = 0.0001). The HR for a failed pancreas graft was 3.51 in SPK and 4.17 for PAK (p = 0.0001). In PTA a failed pancreas graft did not have a direct impact on patient survival. SPK and PAK patients older than 44 yr at the time of transplants also showed an increased mortality risk, but at the same time the risk of immunological graft loss was significantly decreased for those patients. TAC&MMF remained the dominant maintenance immunosuppressant for 2000-2004 US cases (approximately two-third) in all three categories and with this regime 1-year GSRs were > or =80% in all three recipient categories. The results were comparable (> or =83% 1-year GSR) for patients (approximately 10%) treated with Sirolimus (SIR) under various protocols. In regard to non-US pancreas transplants, even for 2000-2004 the overwhelming majority continued to be in the SPK category (91%), with 1-year patient, kidney and pancreas survival rates of 94, 92, and 87%. Solitary transplants are still very rarely done outside the US. Non-US PAK GSR at 1 yr was 85%, non-US PTA GSR at 1 yr was 76%. In summary, with the new advancements in immunosuppression and changes in surgical techniques the outcomes in patient survival and pancreas transplant graft function continue to improve even with an increasing proportion of high risk patients in all three categories.