Introduction: Fractional CO2 laser therapy is used to treat fibrosing conditions similar to Peyronie’s disease (PD). The aim of the study was to evaluate the safety and efficacy of using a fractional CO2 laser in the management of chronic phase PD. Methods: This was a single-site, non-randomized, open-label study using a fractional CO2 laser. Subjects underwent three treatment sessions every six weeks with a fractional CO2 device. Topical triamcinolone was applied immediately after each treatment. Between treatments, patients performed penile modeling three times daily. Penile curvature assessments, self-reported questionnaires, and adverse event screenings were completed at baseline, 24 weeks, and at 52 weeks. Results: Five patients were included in the study. The median baseline penile curvature was 37.0° (interquartile range [IQR] 33.0°, 53.0°), and at 52 weeks, this had reduced to a median curvature to 28.0° (IQR 17.50°, 44.0°, p=0.03), representing a median reduction in penile curvature by 24.3% (IQR 17.0%, 47.5%). The International Index of Erectile Function Overall scores were comparable at baseline and at 52 weeks (median: 59.0, IQR: 42.5, 66.5 vs. median: 60.0, IQR 53.5, 70.0 respectively, p=0.81). Patients did report significant improvement in overall Peyronies’ disease questionnaire (PDQ) scores from baseline to 52 weeks after laser treatment (median 26.0, IQR15.0, 29.5, vs. median: 14.0, IQR 7.0, 22.50, respectively, p=0.03). Four patients reported self-limiting side effects immediately after laser therapy that resolved spontaneously within two weeks. Conclusions: Fractional CO2 laser therapy may serve as a well-tolerated and minimally invasive therapy for PD in the future, with results at 52 weeks being encouraging.