Hypertrophic scar could be associated with several complications that interfere with patient daily activities, physical and psychological health and impact patient quality of life. Several therapeutics and maneuvers are used for treatment of hypertrophic scar with variable success and side effects. We aim to evaluate safety and efficacy of fractional carbon dioxide laser on treatment of hypertrophic scar both clinically and histopathologically. Hypertrophic scars in each patient of total thirty patients were subjected to random division with sealed envelope into two parts, part A treated with fractional carbon dioxide laser every month for 5 sessions, and part B lift without treatment for control. Hypertrophic scars in each patient were single or multiple, Single scar was more than 15 cm length. Clinical evaluation was done by two blinded dermatologists, using Vancouver Scar Scale (VSS) and Patient and Observer Scar Assessment Scale (POSAS) for each part before, 3 months and 6 months after treatment. Histopathological evaluation was done for each part before and 3 months after treatment by measuring epidermal thickness, collagen area percent, and elastin area percent. The upper significant clinical and histopathological improvement was shown in carbon dioxide laser treated parts than control parts without significant side effects for fractional carbon dioxide laser treatment. Treatment of hypertrophic scar with fractional carbon dioxide laser is beneficial and generally considered safe, with minimal risk of harm when performed with appropriate laser parameters for male and female patients with skin type III and IV, at different ages and different body regions.