Vitiligo is a common multifactorial depigmenting skin disease with an estimated worldwide prevalence of 0.5%-2%. 1 Vitiligo is characterized by the selective destruction of melanocytes resulting in typical milky-white macules. 2 Although the disease has serious psychological effects, it is often dismissed as a mere cosmetic problem. 3 Acral lesions are most likely recalcitrant to the known lines of treatment as well as surgical modalities, 4 this may be related to low density of melanocytes and pilosebaceous follicles compared with non-acral parts areas together with the higher incidence of koebnerization in addition to other physiological differences in the tissue milieu. 5 Majority of topically applied medications have relatively low cutaneous bioavailability owing to the skin's barrier function, especially in acral sites. 6 Ablative Fractional CO 2 laser is an outstanding technology with promising clinical applications due to its capacity to produce numerous, coagulated, microscopic columns surrounded by intact areas of skin. 7 Multiple studies demonstrate that fractional CO 2 laser pretreatment of the skin lesions enhances the absorption of topically applied medications along with adding to the synergic effect of the laser. [8][9][10][11] 5 fluorouracil (5FU) has an immunomodulatory effect in treatment for vitiligo. It has shown good results in combination with Erbium-YAG laser 12-14 and dermabrasion. 15