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Aim: Triclosan is an antiseptic substance that has been shown in preclinical studies to reduce bacterial load in the wound and slow bacterial growth by inhibiting fatty acid synthesis. It is claimed that the coating protects against colonization of the tissue around the suture. This study aimed to compare the safety and efficacy of triclosan-coated polydioxanone versus uncoated polydioxanone sutures for the prevention of surgical site infections (SSIs) following hypospadias repair in children. Methods: The medical records of 550 children who underwent hypospadias repair between 1 January 2014 and 31 December 2023 were retrospectively analyzed. The patients included in the study were divided into two groups. The first group consisted of the patients in whom polydioxanone (PDS II) was used (n = 262), while in the patients of the second group (n = 288), triclosan-coated polydioxanone (PDS Plus) was used for hypospadias repair. Secondary outcomes were defined as the occurrence of early and late complications, the number of readmissions within 30 days after surgery (ReAd), unplanned return to the operating room (uROR), and repeat operations. Results: The median age of all children enrolled in the study was 16 (IQR 14, 20) months. The patients in whom PDS Plus was used for hypospadias repair had a significantly lower number of SSIs than the patients in whom PDS II was used (n = 18 (6.9%) vs. n = 4 (1.4%), p < 0.001). Wound infection led to wound dehiscence in 10 of 18 patients from the PDS II group, while all four wound infections from the PDS Plus group led to wound dehiscence (p = 0.07). The number of postoperative urethrocutaneous fistulas was significantly lower in the patients in whom PDS Plus was used (13.7% vs. 8.3%, p = 0.042). The incidence of late complications did not differ between the study groups: meatal stenosis (p = 0.944), residual chordee (p = 0.107), urethral stricture (p = 0.196), scarring (p = 0.351) and urinary discomfort (p = 0.713). There were no cases of uROR in either group. The ReAd rate was low in both groups (n = 5 (1.9%) vs. n = 2 (0.6%), p = 0.266). The frequency of reoperations was lower in the group of patients treated with PDS Plus than in the group of patients treated with PDS II (11.1% vs. 20.6%; p = 0.03). Conclusion: The use of PDS Plus in hypospadias surgery significantly reduces the incidence of SSI, postoperative fistulas, and reoperation rates compared to PDS II.