There is currently no definitive treatment for vitiligo; various modalities include immune modulators phototherapy and skin camouflage. We investigated the efficacy and safety of topical tacrolimus either as monotherapy or combined therapy in the treatment of vitiligo. Electronic systematic search of the literature was carried out using four major databases. Randomised clinical trials (RCTs) that reported the use of topical tacrolimus in the treatment of human vitiligo have been included in a systematic review and meta-analysis. Meta-analysis was conducted via RevMan, and risk of bias was assessed through the Cochrane quality assessment tool. The protocol was published through PROSPERO (CRD42018112430). A total of 19 studies including 814 patients were included in our systematic review. The random-effects-model meta-analysis of two studies revealed that the tacrolimus and narrowband ultraviolet B (NB-UVB) combination therapy rates is better than NB-UVB alone in inducing >75% repigmentation [RR 1.34 (95% CI: 01.05-1.71), P = 0.02]. Tacrolimus and steroids had similar potency in acheiving >75% repigmentation [RR 1.02 (95% CI: 0.19-5.51), P = 0.98]. Meta-analysis of two studies revealed that the fractional laser and tacrolimus combination therapy is no better than tacrolimus alone in causing >75% repigmentation [RR 2.11 (95% CI: 0.87-5.09), P = 0.10]. Further investigating tacrolimus as mono- or adjuvant therapy for vitiligo is highly recommended. Combining tacrolimus to other treatment options such as steroids, phototherapy and laser may be superior to using tacrolimus alone.