Pediatric endoscopic pilonidal sinus treatment (PEPSiT) has become the new standard of care for pilonidal sinus disease (PSD) in pediatric patients. This study aimed to compare our current wound treatment protocol (laser epilation (LE) and oxygen-enriched oil-based gel dressing) with our previous protocol (silver sulfadiazine spray) and demonstrate its efficacy as means to prevent PSD recurrence in children undergoing PEPSiT. We retrospectively reviewed the data of 87 pediatric patients, 52 boys and 35 girls, with an average age of 17.1 years (range, 12-18) affected by chronic PSD, who underwent PEPSiT over a 24-month period (December 2017-December 2019). The patients were divided into two groups: G1 (n = 47) treated with pre- and postoperative LE and oxygen-enriched oil-based gel dressing; and G2 (n = 40) treated with only postoperative dressing using silver sulfadiazine spray. The two groups were compared regarding the operative outcome, wound-healing time, disease recurrence, wound infections, and other complications. Furthermore, efficacy, safety, and tolerability of LE were assessed in G1. No significant difference emerged between the two groups regarding the median operating time, postoperative pain score, hospital stay length, and time to full daily activities (P = 0.33). The median healing time significantly decreased in G1 (21 days) compared with G2 (28.1 days) (P = 0.001]. The disease recurrence rate was significantly lower in G1 (n = 1, 2.1%) compared with G2 (n = 6, 15%) (P = 0.001), and the wound infection rate was significantly lower in G1 (n = 1, 2.1%) compared with G2 (n = 4, 10%) (P = 0.001). All patients with wound infection were treated with oral antibiotics and, after the resolution of the acute episode, received LE with no further infections (Clavien II). Granuloma of the wound occurred in two G2 patients (5%), who were treated with topical silver nitrate (Clavien II). LE was well-tolerated and without complications in all G1 patients; a median number of 7 LE sessions (range, 4-10) at 4-6 weeks interval was required to achieve definitive hair removal. The results of this study confirmed that our standardized pre- and postoperative wound management, including LE and oxygen-enriched oil-based gel dressing, was extremely safe and effective in reducing PSD recurrence and wound infection rate in pediatric patients undergoing PEPSiT. LE should be routinely offered as adjunctive treatment to all patients who receive PEPSiT and is strongly advocated to be started before surgery and continued after wound healing. More importantly, LE showed to have a role as a preventive modality in patients with recurrent folliculitis or infections at the intergluteal crease. It was also associated with significant improvement and acceleration of wound-healing time. LE and oxygen-enriched oil-based gel dressings were clinically safe and well-tolerated in all patients, with no adverse skin reactions or injuries to both therapies. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.