Background Updates of treatment methods of stable vitiligo are needed to give better outcomes with a shorter duration of treatment. Objective To test the effect of transdermal 5‐fluorouracil (5‐FU) delivery using fractional CO2 (FrCO2) laser versus intralesional 5‐FU injection, with narrow‐band type ultraviolet B (UVB) (NB‐UVB) therapy after both, in the treatment of stable vitiligo. Patients and methods The present study comprised 40 patients with nearly symmetrical stable vitiligo lesions. The left side was treated with FrCO2 laser followed by topical 5‐FU (FrCO2 + 5‐FU), while the right side was treated with 5‐FU intradermal injection. Both procedures were done at 2‐week intervals for 3 sessions followed by 24 sessions of narrow‐band UVB for both sides. Results Repigmentation was demonstrated on the left side of 90% of patients and the right side of 85% of patients. As much as >50% improvement was demonstrated on the left side of 50% of patients, and the right side of 55% of patients. Intralesional 5‐FU showed a statistically significant difference in repigmentation compared to FrCO2 + 5‐FU. Conclusion Both 5‐FU injection and FrCO2 + 5‐FU were effective therapeutic modalities for vitiligo. Patients were more compliant with FrCO2 + 5‐FU.