Synthetic mesh and acellular dermal matrix reinforcement during complex abdominal wall reconstruction (CAWR) have significantly improved outcomes. In an attempt to further improve outcomes, we combined both into a single biosynthetic by suturing a synthetic mesh on top of porcine acellular dermal matrix. Our aim was to review our experience with this new technique. Patients undergoing CAWR with the biosynthetic mesh were reviewed from a prospective database from 2015 to 2018. A total of 39 patients were 56.3 ± 10.9 years old, white (59.0%), and female (74.4%), with 31.9 ± 7.4 kg/m of body mass index. Eight repairs were performed on patients classified as greater than or equal to modified Ventral Hernia Working Group (mVHWG) class 3a, and 41.0% followed a concurrent resection of previously placed mesh. The biosynthetic mesh was placed as an underlay (51.3%) or inlay (46.2%) with primary closure in 51.3% and component separation in 12.8%. Recurrence at 3 years of follow-up occurred in 3 patients (7.7%). Complications within 60 days occurred in 6 patients (15.4%), including 4 soft tissue infections-one requiring explantation, with a total of 2 patients (5.1%) requiring explantation overall. Type 2 diabetes, previous mesh removal, component separation, and mVHWG class 3b independently predicted noninfectious complications. Male sex and mVHWG class 3b independently predicted surgical site infection. No predictors were found for recurrence. Biosynthetic mesh does not seem to increase the risk of early complications and may reduce recurrences and improve long-term outcomes after CAWR.