Objective: The primary objective of this study was to compare the effectiveness of topical calcipotriol versus topical tretinoin in treatment of oral leukoaplakia and oral lichen planus regarding clinical improvement as well as their suppressive effect on salivary MMP-9 level which is considered a prognostic marker for malignant transformation. Materials & Methods: Clinical scores were measured at 0,2 and 4 weeks of treatment with 50 mcg/g calcipotriol in an adhesive vehicle and 0.5% Tretinoin cream applied twice daily for 4 weeks. Also, saliva was collected before and after treatment to compare salivary MMP-9 level using ELIZA kit. Results: Results showed that topical calcipotriol is as effective as topical tretinoin in the clinical improvement of oral hyperkeratotic potentially malignant lesions. Both topical tretinoin and calcipotriol resulted in suppression of salivary MMP-9 level. Therefore, they may have role in monitoring the progress of potentially malignant lesions into carcinoma.