Background: Onychomycosis, a fungal infection of the nail, is considered one of the most prevalent disorders of the nail. Score clinical index of onychomycosis (SCIO) enable comparison of the severity of onychomycosis between nails despite differences in the clinical presentation. Recently fractional CO2 laser and topical antifungal were found to be effective in treating onychomycosis. Aim of the Work: To evaluate the clinical efficacy of fractional carbon dioxide laser combined with topical antifungal in treatment of onychomycosis. Patients and Methods: The present study included 20 patients with toenail and fingernail onychomycosis of all age groups. The affected nails received 3 sessions of laser therapy (Fractional CO2 laser) at 4 weeks intervals and once daily application of topical antifungal (Oxiconazole) available at the market under the name tinox cream. Conclusion: We concluded that fractional carbon-dioxide laser therapy, combined with a topical antifungal agent, is effective in the treatment of onychomycosis. It can treat different types of onychomycosis safely and effectively and is especially suitable for older patients with low immunity or liver and renal dysfunction who are not appropriate candidates for systemic antifungal agents. Thus, it could be considered as an alternative treatment modality.