Background. It has been suggested that deceased donor kidneys could be used to initiate chains of living donor kidney paired donation, but the potential gains of this practice need to be quantified and the ethical implications must be addressed before it can be implemented. Methods. The gain of implementing deceased donor-initiated chains was measured with an algorithm, using retrospective data on the pool of incompatible donor/recipient pairs, at a single center. The allocation rules for chain-ending kidneys and the characteristics and quality of the chain-initiating kidney are described. Results. The benefit quantification process showed that, with a pool of 69 kidneys from deceased donors and 16 pairs enrolled in the kidney paired donation program, it was possible to transplant 8 of 16 recipients (50%) over a period of 3 years. After obtaining the approval of the Veneto Regional Authority's Bioethical Committee and the revision of the Italian National Transplant Center's allocation policies, the first successful case was completed. For the recipient (male, aged 53 y), who entered the program for a chain-initiating kidney with a Kidney Donor Risk Index of 0.61 and a Kidney Donor Profile Index of 3%, the waiting time was 4 days. His willing donor (female, aged 53 y) with a Living Kidney Donor Profile Index of 2, donated 2 days later to a chain-ending recipient (male, aged 47 y) who had been on dialysis for 5 years. Conclusions. This is the first report of a successfully completed, deliberate deceased donor-initiated chain, which was made possible after a thorough assessment of the ethical issues and the impact of allocation policies. This article includes a preliminary efficacy assessment and describes the development of a dedicated algorithm.