Objectives Nerve wraps have been used to potentially decrease perineural scarring and to create a local environment conducive to nerve healing, but no consensus exists on the indications for their use. The primary purpose of this study is to assess the operative indications for using the porcine extracellular matrix (PEM) nerve wrap in the upper extremities at a single center. Methods A retrospective review of all patients that underwent PEM nerve wrapping over eight years by hand and upper extremity surgeons at a single orthopaedic practice yielded 104 procedures in 102 patients for analysis. Results The most common indication for surgery was for nerve wrapping of acute traumatic nerve injuries in 57 patients (55%), most frequently involving lacerations of the hand and forearm. Neurolysis and nerve wrapping for cases of chronic nerve compression with perineural scarring and fibrosis was the second most common indication, involving 41 patients (39%), most frequently for revision carpal and cubital tunnel release surgery. Six patients (5.8%) underwent mass removal or contracture release involving neurolysis with nerve wrapping. Three patients (2.9%) required reoperation, two in the acute group and one in the chronic group. However, there were no cases of nerve wrap rejection or extrusion. Conclusion PEM nerve wrapping was used for various nerve injuries, from acute lacerations to recalcitrant chronic compression and mass excision. Further studies are necessary to determine whether patient outcomes are improved with the PEM nerve wrap. Level of Evidence Level 4