Background: Although keloids of unknown origin can also develop, keloids are a skin disease where the skin expands past the borders of the initial incision. Intralesional triamcinolone (TAC) injections have been demonstrated to lessen related scar pain and itching, decrease scar volume and height, and improve scar pliability. One of calcium channel blockers; verapamil, causes the release of procollagenase, which speeds up the breakdown of scar tissue. As a result, the morphology of fibroblasts changes, TGF-1 apoptosis is induced, the formation of extracellular matrix (ECM) is decreased, and actin filaments are depolymerized. Objective: comparing the efficacy and safety of fractional CO₂ combined with intralesional verapamil versus fractional CO₂ combined with intralesional triamcinolone in the treatment of keloid. Patients and methods: Twenty patients with keloids participated in this investigation. They were chosen from the Dermatology Department's Outpatient Clinic at Mansoura University Hospital. Patients with two keloid were recruited; one keloid was treated with fractional CO₂ with intralesional verapamil (arm A) and the other was treated with fractional CO₂ with intralesional triamcinolone (arm B). Results: In the fractional CO₂ laser with intralesional triamcinolone and verapamil groups, there was a statistically significant decrease in the height and surface area of keloid before and after treatment. The reduction of lesion height was significantly higher in fractional CO₂ laser with intralesional triamcinolone group in comparison with verapamil group (P = 0.003). Conclusion: Combined fractional CO₂ laser with intralesional triamcinolone therapy showed better clinical improvement compared to combined fractional CO₂ laser with intralesional verapamil therapy, but with more adverse effects.