Treatment of vitiligo represents a highly therapeutic challenge in spite of the continuous development of new modalities. Combination therapies of vitiligo can help improve treatment response, and reduce recurrence potential. To compare the efficacy and adverse effects of microneedling combined with ٥-fluorouracil, pimecrolimus, and trichloroacetic acid (TCA) in the treatment of localized, stable vitiligo. The study included 75 patients with non-segmental, stable vitiligo who were randomly assigned to three equal groups: group received a combination of microneedling and -FU, group 2 received microneedling and pimecrolimus, and group 3 received microneedling and TCA. The procedure was done every 2 weeks for a maximum of six sessions. Com- bined microneedling and TCA was associated with the highest + 5-fluorouracil, and lastly combined microneedling + pimecrolimus. The difference between the three groups was statistically significant in favor of the combined microneedling and TCA. Pain, erythema, post-inflammatory hyperpigmentation, infection, and scarring were variably reported adverse effects in the three groups. Combination therapy seems to be a promising modality for the treatment of vitiligo. Combined microneedling and TCA is superior to combined microneedling with either-fluorouracil or pimecrolimus.