Introduction: Deep second-degree burn injuries are the most challenging situations for the burn surgeon in the treatment of adult cases. While waiting for spontaneous closure increases the risk of hypertrophic scar and keloid, early excision and grafting pose the risk of donor site wound and permanent color differences. Unlike many studies in the literature, the current study was planned in a way to minimize factors other than burn wounds to investigate the effect of adding hyperbaric oxygen (HBO2) therapy to conventional treatment in deep second-degree burn wounds. Material and Methods: This prospective observational study included patients with burn injuries who underwent conventional treatment alone and those who underwent conventional plus HBO2 treatment performed by a single experienced surgeon and who met the study criteria. Results: Thirty-eight patients completed the study. Mean burned total body surface area (TBSA) was. 9.22 ± 3 43% (range 5% to 20%). There was no difference between the two groups in terms of age, burned TBSA, and burn etiology. The need for surgery and grafting was lower in patients who received HBO2 in addition to conventional treatment (p=0.003 and p=0.03, respectively). The patients in the HBO2 group had a shorter hospital stay, and their wounds epithelialized in a shorter time (p=0.169 and p≺0.001, respectively). They also had a higher satisfaction level and lower treatment cost (p=0.03 and p=0.36, respectively). Discussion: The results of this prospective study, in which co-factors were eliminated, showed that adding HBO2 to the conventional treatment of deep second-degree burns had a significant positive effect on patient outcomes, as well as reducing treatment costs.