Prosthetic reinforcement reduces the recurrence rate of large paraesophageal hernias (PEH), but the use of synthetic or biosynthetic mesh in the repair remains controversial. PEH repair has reported recurrence rates of 12% to 42%, and primary repair of PEH by suture closure under tension is at high risk of disruption. Synthetic mesh use in large PEH repair has shown to reduce recurrence but can lead to problems including mesh erosion, ulceration, stricture, and dysphagia. The objective of this study was to examine the long-term safety and efficacy of Strattice biologic mesh, a porcine acellular dermal matrix, in crural reinforcement of laparoscopic large PEH repair. Thirty-five patients with symptomatic PEH (>5 cm) were consented to receive Strattice for PEH repair. Patients were seen in clinic preoperatively, at surgery, and 2 weeks, 6 months, and 12 months postoperatively. Patients were given a standard subjective reflux test at each visit and a 12-month barium swallow X-ray to test for recurrence. Hernia recurrence was documented in 14.3% of cases by the end of the 1-year follow-up. Symptoms improved in 75% to 100% of patients by 6 months, and 33% to 100% of patients were still reporting symptom improvement at 12 months. Strattice mesh in PEH repair results in similar outcomes to other absorbable meshes, and the recurrence rate is within the 12% to 42% range of recurrences reported in studies outside of our institution. The use of Strattice mesh in large PEH repair had results similar to other biomaterial meshes and successfully decreased patients’ symptom scores through surgical intervention.