Introduction: Mesh has become the preferred method due to its ability to integrate with the host’s tissue, reducing recurrence rates compared to primary suture repairs. While synthetic mesh reduces recurrence rates, it may lead to inflammation and infection. To evaluate its performance, this study aims to assess the short-term outcome following ventral hernia repair with biosynthetic mesh. Background: In Ventral Hernia Working Group Grade 3 hernias, which are often contaminated due to factors like prior wound infections, the presence of a stoma, or gastrointestinal tract violations, the heightened risk of infection poses significant challenges. In such cases, the success of mesh repair is jeopardized by potential contamination, complicating the surgical process; prompting consideration of resorbable or biological meshes despite higher costs. A recent advancement is biosynthetic mesh, notably poly-4-hydroxybutyrate, which offers strength comparable to polypropylene mesh and undergoes resorption. However, it retains only 70% strength after 12 weeks, potentially contributing to recurrence. Its efficacy in contaminated sites requires further exploration. Methods: We conducted a retrospective cohort study to thoroughly assess the potential complications following ventral hernia repair. This study will include all patients whose ages are >16 and underwent either open or laparoscopic ventral hernia repair with a biosynthetic mesh at King Abdulaziz Medical City, Saudi Arabia, Riyadh National Guard Health Affairs. The study period extends from January 2020 to December 2023. The study data were extracted from patients’ medical records through the BestCare system. Results: The mean age of our cohort was 58.65 with body mass index 39.6 when looking at comorbidities diabetes mellitus and HTN were the most common comorbidities with 32% affected with diabetes, and 39% affected with hypertension. The most common hernia type observed in our study was incision hernia accounting for 36% of all hernia types followed by inguinal hernia 24.6%. Complications were assessed at 4 time intervals of 1, 3, and 6 months and 1 year. The majority of the patients with complications presented at the 1st month with seroma accounting for 2.2% followed by surgical site infection (SSI) 1.8% and only three patients had 1-year postoperative recurrence. Discussion: The long-term effects of using a permanent synthetic mesh have not been fully understood. However, examining the outcomes associated with absorbable mesh can provide a useful framework for discussing potential risks with patients. Reported outcomes include rates of hernia recurrence and various surgical site occurrences requiring intervention, such as SSI, seroma, wound dehiscence, skin necrosis, hematoma, and fistula. It is important to note that this study is a retrospective cohort study with long-term follow-up, rather than a randomized controlled trial. In addition, other peer-reviewed studies have assessed alternative resorbable synthetic or biologic hernia repair materials, including TIGR® Matrix, Gore® Bio-A®, and Strattice™. Conclusion: In short, our results are comparable to the published reports. No statistically significant improvement in quality of life or reduction of pain was observed. Few patients report the lasting presence of mesh sensation. Results of the biosynthetic mesh after longer periods of follow-up on recurrences and remodeling will provide further valuable information to make clear recommendations.