Fractional CO laser has been proposed recently to be effective and well tolerated in patients with refractory vitiligo. In this preliminary, prospective study, 21 patients with multiple, localized, refractory, non-segmental vitiligo lesions were randomized to receive either tacrolimus ointment plus 308 nm excimer lamp (control), with or without the addition of fractional CO laser. There was no statistically significant improvement in the repigmentation on the laser side compared to the control side. Treatment was generally well-tolerated; only localized adverse effects were noted. Overall the triple combination therapy was not superior to tacrolimus ointment plus 308 nm excimer lamp. Treatment failure may reflect insufficient penetration of tacrolimus ointment through the holes created by fractional CO laser on the skin.