A bioabsorbable tissue scaffold of porcine submucosal small intestine extracellular matrix (Surgisis Gold [SIS]; Cook Biotech Inc, West Lafayette, Ind) mesh is safe and effective for ventral hernia repair. Retrospective case series at a university teaching hospital. Fifty-three consecutive patients having 8-ply SIS mesh repair of ventral abdominal hernias. Early complications, reoperation, hernia recurrence, mesh or wound infection, or reaction. Outcomes reported and compared on an intention-to-treat basis. Patients were stratified by wound class: clean, clean-contaminated and contaminated, or dirty. Median follow-up was 14 months (range, 2-29 months) during which there were 22 complications (41%), 17 early reoperations (32%), 13 partial dehiscences (21%), 6 mesh reactions (11%), and 9 recurrent hernias (17%). Seven recurrent hernias (78%) in critically ill, patients with dirty wounds had the SIS mesh removed owing to infection or reoperation. In patients without SIS mesh removal or debridement, 1 (2.2%) of 44 developed a recurrent hernia at 6 months. Patients with dirty wounds were more likely to need early reoperation (P<.001), develop a complication (P<.01), partial wound dehiscence (P<.05), or recurrent hernia (P<.01) compared with patients with clean wounds. Critically ill patients were more likely to have hernia recurrence (P<.05), early reoperation (P<.001), and postoperative complications (P<.05). Eight-ply SIS mesh is safe in clean and clean-contaminated hernia repair with satisfactory short-term outcomes. However, delayed wound infection, repeated operation, and mesh debridement warrant cautious use of SIS mesh in critically ill patients and those with dirty wounds.