Islet transplantation usually requires multiple donors, which can be a limiting factor given scarce resource. In this study, we aimed to identify factors associated with successful single-donor transplantation. In our center, 11 type I diabetic patients received islet transplantation following the CIT07 protocol in the past 6 years. Islets were isolated under the guideline of CIT consortium. All recipients became insulin independent post transplantation. Insulin independence was achieved in 7 patients with one donor, while a second transplantation was needed for the other 4 recipients. In the single-donor group, 2 patients have been free from insulin treatment for over 5 years. The characteristics of donors, isolated islets of the initial transplantation and recipients were examined. No statistical difference was observed in donor characteristics and isolated islet functions between the two groups. The total islet equivalent (IEQ) of the single-donor group was significantly higher than the two-donor group (633275±165697 vs 456370±28907, p<0.05). The volume (ml) of high purity (>70%) islet was also significantly higher in the single-donor group (1.9±0.7 vs 0.9±0.1, p<0.01). Statistically significant correlation was observed between high purity islet volume and total IEQ (r=0.73, p=0.01), suggesting that the volume can be used as a measure of islet yield. The amount of transplanted islet (IEQ per kg recipient body weight) in the single-donor group is significantly higher comparing to those in the two-donor group (9088±759 vs 6388±524, p<0.05). Multiple linear regression analysis showed that the number of donors required for a successful transplantation is negatively correlated to quantity of transplanted islets (p<0.05) and positively correlated to recipient age (p<0.05). All recipients younger than 40 years old achieved insulin independence with a single-donor infusion while older recipients required higher quantity of islets. No statistical difference was observed in the recipients' pre-transplant characteristics and diabetic status between the two groups. Our results suggest that quantity of islet transplanted and age of recipients are two key factors in predicting successful single-donor transplantation. We hope our data can provide direction in achieving successful single-donor transplantation.