Transversus abdominis release (TAR) may provide an optimal plane for mesh placement for large ventral hernias requiring medial myofascial flap advancement. Long-term outcomes of TAR for large ventral hernia repair (VHR) remains under-studied. This study aims to assess longitudinal clinical outcomes and quality of life (QoL) following large VHR with TAR and resorbable biosynthetic mesh. Retrospective review of clinical outcomes and prospective QoL was performed for patients undergoing VHR with poly-4-hydroxybutyrate mesh and TAR from 2016 to 2021. Patients with ≤ 24months of follow-up, defects ≤ 150cm2, and parastomal hernias were excluded. Cost-related data was collected for each patient's hospital course. QoL was compared using paired Wilcoxon signed-rank tests. Twenty-nine patients met inclusion criteria. Median age and BMI were 61years (53.2-68.1years) and 31.4kg/m2 (26.1-35.3kg/m2). Average hernia defect was 390cm2 ± 152.9cm2. All patients underwent previous abdominal surgery and were primarily Ventral Hernia Working Group 2 (58.6%). Two hernia recurrences (6.9%) occurred over the median follow-up period of 63.1months (IQR 43.7-71.3months), with no cases of mesh infection or explantation. Delayed healing and seroma occurred in 27 and 10.3% of patients, respectively. QoL analysis identified a significant improvement in postoperative QoL (p < 0.005), that continued throughout the 5-year follow-up period, with a 41% overall improvement. Cost analysis identified the hospital revenue generated was approximately equal to the direct costs of patient care. Higher costs were associated with ASA class and length of stay (p < 0.05). Large VHR with resorbable biosynthetic mesh and TAR can be performed safely, with a low recurrence and complication rate, acceptable hospital costs, and significant improvement in disease-specific QoL at long-term follow-up.