BACKGROUND: Vitiligo is an autoimmune disease with a prevalence of 1.22% in Egypt. Intralesional steroids use in localized vitiligo treatment still a matter of debate. Fluorouracil was tried in vitiligo treatment after lesion dermabrasion, ablative laser, or micro-needling. The study aimed to compare the efficacy of intradermal fluorouracil and triamcinolone acetonide without any adjuvant therapy in localized vitiligo treatment. PATIENTS AND METHODS: Sixty patients with localized non-segmental stable vitiligo were assigned randomly and equally into groups. Patients subjected to intradermal injection of either fluorouracil (50 mg/mL), triamcinolone acetonide (3 mg/mL) or an equal mixture of both drugs. All patients had four treatment sessions every 2 weeks were followed up for 6 months. RESULTS: Intradermal fluorouracil showed the best overall improvement (median 52.27, IQR 36.25-68.18) when compared with triamcinolone (median 13.86, IQR 3.83-33.32) and the drug mixture (median 17.15, IQR 7.48-41.67). During follow-up, the vitiliginous patches continued to repigment for 6 months in fluorouracil and the drug mixture groups. The improvement stopped 1 month after the last session in the triamcinolone group. CONCLUSION: The intradermal fluorouracil injection is an effective treatment of localized vitiligo. The intradermal steroid has a short-acting therapeutic effect, but the mixture of drugs added no therapeutic effect. © 2018 Wiley Periodicals, Inc.