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BACKGROUND: Alopecia areata (AA) is a chronic inflammatory disease that affects the hair follicles and sometimes the nails. It usually presents as a single or multiple patches of hair loss on the scalp, but any hair-bearing skin can be involved. AA treatment depends on the severity and extent of the disease. OBJECTIVE: To evaluate the efficacy of combined fractional CO2 (FCO2) laser with topical minoxidil 5% solution versus topical minoxidil 5% solution alone in the treatment of AA. PATIENTS AND METHODS: The study included 150 patients with AA. The patients were collected from outpatient clinics of the Dermatology and Venerology Department, Tanta University Hospitals. Patients were divided into three groups; 60 patients were treated with topical minoxidil 5% solution, 60 patients were treated with FCO2 laser combined with topical minoxidil 5% solution, and the third group of 30 patients represented the control group treated with topical saline. RESULTS: Compared to the placebo group, there was a statistically significant improvement in hair growth in the combination group and minoxidil group. In the combination group, 80% of patients showed excellent improvement, 13.3% of patients showed very good improvement, and 6.7% of patients showed good improvement. In the minoxidil group, 53% of patients showed excellent improvement, 40% of patients showed very good improvement, and 6.7% of patients showed good improvement after 3 months of therapy. Side effects were minimal and transient in both groups. CONCLUSION: Topical minoxidil 5% solution either alone or in combination with FCO2 laser could be considered a safe and tolerable method for AA treatment.