Background Although the frequency of biological valve use in treating aortic valve disease is increasing, the critical limiting factor, “structural deterioration,” remains unresolved. Analysis of long-term outcomes after implantation of cryopreserved aortic allografts will yield further information related to the durability of the aortic allograft, possibly suggesting mechanisms underlying or strategies to prevent or treat the structural deterioration of biological valve substitutes. Methods A total of 840 cryopreserved aortic allografts implanted in the last 35 years were reviewed with clinical follow-up completed in 99% of the consecutive series. By June 2010, 285 implanted allografts had been surgically explanted, 288 patients died before allograft removal, and 267 patients are under continued follow-up. Results Cryopreserved aortic allografts were durable for more than 15 years in the middle-aged and older patient population. The estimated median time until structural deterioration was 20 years post-implantation, and 2 allografts have been functioning well for more than 30 years. Structural deterioration was independently related to the young age of the recipient, elderly age of the donor, severe obesity in the recipient, history of blood transfusion in the recipient, and full-root implantation technique. Infection of the implanted allograft necessitating reintervention rarely occurred. Reintervention for the allograft demonstrated 2% in-hospital mortality. Conclusions Cryopreserved aortic allografts were durable for more than 15 years. Structural deterioration of aortic allografts was related to multiple factors. The age of the recipient and the donor, obesity and blood transfusion history of the recipient, and implantation technique were identified as the most important factors contributing to allograft failure.