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<i>Background and objectives</i>: Vitiligo is an acquired chronic and idiopathic skin disorder, characterized by selective loss of melanocytes and resulting in a cutaneous depigmentation. Treatment for vitiligo remains a challenge for dermatologists; thus, it is frustrating both for physicians and patients. The objective of this study was to evaluate a combination treatment characterized by the use of a leukocyte-rich platelet-rich plasma, which is particularly rich in monocytes (defined here as monocyte-rich PRP), in combination with a 1927 nm fraxel laser and a 308 nm excimer laser. <i>Materials and Methods</i>: Treatment with monocyte-rich PRP combined with 1927 nm fraxel laser and 308 nm excimer laser was performed in nine sessions in 80 days and the median follow-up of the patients was 10 months. A total of 27 Caucasian patients were included in the present study. The median age of patients was 41 years, ranging between 20 and 69 years. <i>Results</i>: A re-pigmentation occurred in 16 cases (59%) with a reduction of the Vitiligo Extent Score (VES) and absence of re-pigmentation in untreated areas. Performing a rank correlation between VES and re-pigmentation in the treated areas, we found that there was a significant correlation (<i>p</i> < 0.0001). The presence of progressive vitiligo (<i>p</i> = 0.1) and the anatomic areas (<i>p</i> = 0.1) did not influence the treatment. Untreated areas did not show any improvement of the depigmented lesions, except in one case (<i>p</i> < 0.0001). <i>Conclusions</i>: in this report, we show for the first time how PRP rich in monocytes, in combination with laser therapies, gives a long therapeutic response, which persists even after 10 months of follow-up.