Objectives: To investigate whether daily systemic and/or topical medication contributes to the development of oral lichen planus (OLP) lesions. Study Design: The study involved 110 OLP patients and 76 control subjects, matched by age, race and sex. The analyzed data included medical records, drug intake and topical medication. Criteria for analysis of drug intake included: (1) ATC-code drug classification; (2) number of different drugs used daily in the categories of monopharmacy (1 drug), minor polypharmacy (2 4 drugs), and major polypharmacy (> 5 drugs); and (3) drugs implicated in lichenoid reactions (DILRs). Results: Sixty (54.5%) of the 110 OLP patients reported daily medication (prior to the appearance of the OLP lesion) compared to 52 (68.4%) of the 76 control subjects. No statistical difference was found between the two groups in terms of systemic diseases, number of medicated individuals in the categories of mono- and polypharmacy, nor use of DILRs (P > 0.05). Regarding the clinical forms and site of involvement, a statistically significant difference was only found for the clinical erosive form of OLP, seen more frequently in non-DILR (P = 0.04) and nonmedicated OLP patients (P = 0.02) than in DILR OLP patients. Daily use of topical oral medication was reported by 2 (1.8%) OLP patients and 1 (1.3%) control subject. Conclusions: It seems that the use of systemic medication does not lead to a significant increase in the incidence of OLP lesions. For their part, lichenoid drug reactions are likely to occur only in a very low percentage of patients. © Medicina Oral S. L.