Cryopreserved amnion tissues derived from amniotic membrane/umbilical cord (AM/UC) have been used extensively in ophthalmology for minimizing postoperative inflammation, pain, and adhesion formation following various surgical procedures. There is limited data in the current literature regarding the use of amnion tissue product in foot and ankle surgery. The purpose of this retrospective study is to report the short-term safety profile after in vivo application of cryopreserved AM/UC tissue use in foot and ankle surgery. A retrospective consecutive case series was performed for cases where amnion tissue was used with a minimum follow-up of 120 days between 2011 and 2012. The clinical outcomes of interest were postoperative infections, delayed or nonhealing wounds, adverse surgical site reactions, and repeat surgery for formal irrigation and debridement. One hundred twenty-four patients qualified for inclusion. Cryopreserved AM/UC tissue was introduced into the surgical wound and placed adjacent to the compromised and repaired tendons, most frequently in peroneal and Achilles tendon repairs. In this level IV consecutive case series cohort, there was an overall wound complication rate of 5.64%, with a re-operation rate of 1.6% (2/124). In each of these cases, patients had an irrigation and debridement with ultimate successful wound healing. The results of this study demonstrate that the use of amnion tissue in the foot and ankle setting is safe with a decreasing trend in overall complication rates compared with historically published norms.