Background: Frey’s syndrome is a well-known complication of parotid surgery; its prevention may be achieved by the use of an interpositional barrier between the overlying flaps and the exposed parenchymal bed of parotid gland. The aim of this study was to retrospectively evaluate clinical outcomes with and without the interpositional placement of a porcine dermal collagen graft (PDCG) for prevention of syndrome occurrence. Methods: We conducted a 20-year retrospective study including the patients who had undergone “formal” (superficial, total, or subtotal) parotidectomies for benign pathologies. The inclusion criteria also involved patients that were (i) regularly monitored about clinical symptoms related to syndrome, and (ii) examined with Minor starch-iodine test. The severity of the diagnosed syndrome was retrospectively evaluated according to the grading score system of Luna-Ortiz. To assess group differences in terms of the extent of dissection in operating sites, we estimated the tumor and histological specimen volumes using the available dimensions. Results: We included 73 patients who had undergone 76 formal parotid surgeries. The surgical sites were divided into 2 groups: (1) Group A consisted of 44 sites that were reconstructed with a SMAS flap, and (2) Group B, comprised 32 sites where a PDCG was additionally applied as an artificial preventive barrier. At a mean follow-up of 26.3 months, a significantly lower incidence of clinically diagnosed Frey’s syndrome was found after the use of dermal collagen interpositional barrier ( P = .031). Specifically, subjective symptoms were reported at an incidence of 31.8% in Group A and 6.7% in Group B. Minor’s test was positive at an incidence of 59.09% in Group A and 21.87% in Group B ( P = .004, 95% CI). Severe Frey’s syndrome was observed in 31.82% of the patients of Group A and in 3.12% of the patients of Group B ( P = .002, 95% CI). Since there were no statistical significant differences between the volumes of the removed tumors and the excised histological specimens, the extent of dissection was not proved to influence the occurrence of Frey’s syndrome in the compared groups, Conclusion: Porcine dermal collagen is a safe, practical, and useful means for parotid reconstruction, since it seems to contribute in prevention of Frey’s syndrome when increased amount of glandular tissue has to be removed. Additional randomized controlled studies with bigger samples are required to better assess the PDCG use in parotid surgery.