Background: There is no standard protocol for treating oral lichen planus. We need to develop potent alternative immunosuppressive agent to benefit the patients. Aim: To investigate the efficacy of 0.1% tacrolimus with Colgate Oraguard-B paste for the treatment of patients with oral lichen planus. Methods: One hundred patients with clinical evidence of the lesion of oral lichen planus followed by histopathological confirmation seeking care at outpatient department were included in the study. Patients were provided with 0.1% tacrolimus ointment with Colgate Oraguard-B paste as the study medication. Reassessment was done from 3 months to 4 months, with follow-up of 2 years and 6 months. Results: Mean values of pre and post VAS (Visual Analogue Scale) for erosive and atrophic forms of oral lichen planus were 9.35±1.02, 2.96±0.24 and 7.82±0.56, 1.71±0.22 respectively. Similarly mean pre and post VAS scores for reticular and mixed forms of oral lichen planus were 4.16±0.44, 1.32±0.34 and 7.36±0.59, 3.33±0.48 respectively. Statistically significant results were obtained between pre and post treatment values on the Visual Analogue Scale among all forms of oral lichen planus. Conclusion: Topical tacrolimus ointment 0.1% with Oraguard-B paste showed us encouraging results for symptomatic Oral lichen planus. Clinical improvement was achieved in about a month’s treatment course.