BACKGROUND AND OBJECTIVES: The aim of this study was to compare the efficacy and safety of fractional carbon dioxide (CO ) laser versus carboxytherapy in treatment of striae distensae. STUDY DESIGN/MATERIALS AND METHODS: This study was conducted on forty female patients with striae distensae on the abdomen. Patients were selected and divided randomly into two matched groups; group I was treated with fractional CO laser resurfacing and group II with carboxytherapy. Assessment and evaluation of the results were done by comparing photographs and the Global Aesthetic Improvement Scale (GAIS). RESULTS: Pregnancy, obesity, and long-term steroid use were the most common causes of striae in both groups. Both groups showed a statistically significant improvement in both the width and length of striae with no statistically significant difference between them. Patients' satisfaction was comparable in both groups. Pain and post-inflammatory hyperpigmentation were the two most common side effects in group I while bruising at the injection site was the most common in group II. CONCLUSIONS: Both modalities could be effective in management of striae distensae. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.