Background: Nail affection is estimated to affect about 85% of cases with psoriasis vulgaris (PV) in their lifetimes and is frequently accompanied by severe disease and impairment of quality of life (QoL). Tacrolimus (0.1-0.03%) ointment was demonstrated to be efficient in PV owing to its immunosuppressive characteristics. Regarding its therapeutic effect on nail psoriasis (NP), it appeared to be similarly efficient on nail bed and matrix lesions without having extensive adverse events. Objectives: Since previous trials on topical tacrolimus in treatment of NP was concentrating only on the higher concentration (0.1%), which is more expensive and frequently not available in many developing countries, the present study aimed to evaluate and compare the efficacy and safety of topical tacrolimus by the two concentrations (0.1% and 0.03%) in treatment of nail psoriasis. Patients and Methods: This randomizedcomparative study comprised 50 patients with nail psoriasis; half of them were treated by tacrolimus 0.1% (group A) and the other half by tacrolimus 0.03% (group B). Five patients from each group were lost follow up so the statistics involved only 20 cases in each group, the assessment of disease severity was conducted by using Nail Psoriasis Severity Index (NAPSI) score. Results: There was a statistically significant decrease in NAPSI score starting 1 month after initiation of treatment in both groups. Although improvement frequency was better in group A than group B but the difference was not statistically significant. Conclusion: both concentrations of topical calcineurin inhibitors (0.1% and 0.03%) showed high statistically significant improvement in NP after six months of treatment. Additionally topical calcineurin inhibitors demonstrated no side effects, so they are safe and tolerable drugs in the context of NP treatment.