Objective: This study was carried out to provide comparative analysis of the efficacy of triamcinolone acetonide and tacrolimus in treating Oral lichen planus, based on clinical and histological evaluations. Materials and methods: The study group comprised of 60 Oral lichen planus subjects of either sex in the age range of 25 to 60 years. The participants were randomly assigned to two groups: the triamcinolone acetonide group A (n=30) and the tacrolimus group B (n=30). The patients in the group A were applied with triamcinolone acetonide (0.1%) twice daily after food for a period of eight weeks and the patients in the group B received topical tacrolimus (0.1%) twice daily for a period of eight weeks. The clinical parameters recorded at each visit included burning sensation, size of lesion and erythematous areas. The data collected was subjected to appropriate statistical analysis. Results: In the triamcinolone acetonide group, the mean pain score decreased from 6.2 ± 1.8 at baseline to 2.1 ± 1.5, mean burning sensation score decreased from 6.4 ± 2.0 at baseline to 2.8 ± 1.7 andmean lesion size decreased from 23.5 ± 10.3 mm² at baseline to 7.5 ± 4.6 mm² after eight weeks of treatment (p<0.001). Similarly, in the tacrolimus group, the mean pain score decreased from 6.4 ± 1.7 at baseline to 2.4 ± 1.6, mean burning sensation score decreased from 6.6 ± 2.0 at baseline to 2.9 ± 1.8 and mean lesion size decreased from 24.1 ± 9.7 mm² at baseline to 7.8 ± 4.5 mm² after eight weeks of treatment (p<0.001). The Mann-Whitney U test showed no significant difference in clinical parameters between the two treatment groups. However, the histological parameters were significantly better in the tacrolimus group compared to the triamcinolone acetonide group (p<0.05).The standard deviation values for all clinical and histological parameters were lower in the tacrolimus group compared to the triamcinolone acetonide group. This suggests that the treatment effect of tacrolimus was more consistent across all patients. The p values for all parameters were highly significant (p<0.001), indicating a strong treatment effect in both groups. Conclusion: Tacrolimus may have a more potent anti-inflammatory effect compared to triamcinolone acetonide.