<p>Vitiligo is a chronic depigmenting condition that causes amelanotic macules and patches on the skin. Despite various treatment options, treating vitiligo is a challenge. This study aimed to evaluate the combination of laser CO₂ fractional and narrow-band ultraviolet B (NB-UVB) versus NB-UVB monotherapy in vitiligo patients. This was a prospective, self-controlled, and randomized trial. Ten patients with symmetrical vitiligo lesions on both sides of their body and who had a history of insufficient response to conventional therapies were included in this trial. Group A received three sessions of fractional CO₂ laser at 1-month intervals during NB-UVB phototherapy which was performed three times a week for three months. Patients in group B only received phototherapy same as group A. The primary endpoint was the repigmentation rate. The mean age was 34.40 ± 11.93 years (range of 19–63). After the intervention, repigmentation was better in group A and the difference was statistically significant (<i>P</i> = 0.025). Patients in group A showed a better reduction of VASI score than group B (39.12 ± 27.81 Vs. 44.45 ± 30.77), although it was not statistically significant (<i>P</i> = 0.518). VETF and VIDA outcomes were slightly better in Group A than B, but it was not statistically significant (<i>P</i> = 0.317 and <i>P</i> = 0.180, respectively). The results of this study indicated that combining fractional CO₂ laser with NB-UVB is superior to NB-UVB monotherapy, providing a promising modality in vitiligo patients.</p>