BACKGROUND: Long-term resorbable mesh represents a promising technology for ventral and incisional hernia repair (VIHR). This study evaluates poly-4-hydroxybutyrate mesh (P4HB; Phasix Mesh) among comorbid patients with CDC class I wounds. STUDY DESIGN: This prospective, multi-institutional study evaluated P4HB VIHR in comorbid patients with CDC class I wounds. Primary outcomes included hernia recurrence and surgical site infection. Secondary outcomes included pain, device-related adverse events, quality of life, reoperation, procedure time, and length of stay. Evaluations were scheduled at 1, 3, 6, 12, 18, 24, 30, 36, and 60 months. A time-to-event analysis (Kaplan-Meier) was performed for primary outcomes; secondary outcomes were reported as descriptive statistics. RESULTS: A total of 121 patients (46 male, 75 female) 54.7 ± 12.0 years old with a BMI of 32.2 ± 4.5 kg/m 2 underwent VIHR with P4HB Mesh (mean ± SD). Fifty-four patients (44.6%) completed the 60-month follow-up. Primary outcomes (Kaplan-Meier estimates at 60 months) included recurrence (22.0 ± 4.5%; 95% CI 11.7% to 29.4%) and surgical site infection (10.1 ± 2.8%; 95% CI 3.3 to 14.0). Secondary outcomes included seroma requiring intervention (n = 9), procedure time (167.9 ± 82.5 minutes), length of stay (5.3 ± 5.3 days), reoperation (18 of 121, 14.9%), visual analogue scale-pain (change from baseline -3.16 ± 3.35 cm at 60 months; n = 52), and Carolinas Comfort Total Score (change from baseline -24.3 ± 21.4 at 60 months; n = 52). CONCLUSIONS: Five-year outcomes after VIHR with P4HB mesh were associated with infrequent complications and durable hernia repair outcomes. This study provides a framework for anticipated long-term hernia repair outcomes when using P4HB mesh.