Tehran University of Medical Sciences Journal of Pharmaceutical Care 2322-4630 10 1 2022 03 28 34 39 Atefeh Eshghinejad Pharmacy Student's Research Committee, School of Pharmacy, Isfahan University of Medical sciences, Isfahan, Iran Elham Panahandeh Pharmacy Student's Research Committee, School of Pharmacy, Isfahan University of Medical sciences, Isfahan, Iran Melika Memarfar Pharmacy Student's Research Committee, School of Pharmacy, Isfahan University of Medical sciences, Isfahan, Iran Rasool Soltani Department of Clinical Pharmacy and Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. Fatemeh Shafiee Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. 2022 02 09 2022 03 19 Several evidence have shown the beneficial effects of pentoxifylline in the improvement of oral aphthous ulcers. However, the data in this regard are sparse. So, the efficacy and safety of pentoxifylline in oral route was systematically reviewed to elucidate its effects on the size and number of ulcers, as well as the healing time and recurrence frequency in RAS patients. PubMed (Medline), Web of Science, Scopus, ScienceDirect, Cochrane Library, ProQuest, and Clinicaltrial.gov were searched for related articles. The investigated outcomes were pain level, the size and number of ulcers, the frequency of recurrence, the healing time, and finally the pentoxifylline related side effects. Only 6 related study that investigate the efficiency of Pentoxifylline on RAS (n =107) were identified. Decreasing in the pain level, improving the ulcer size and number were establishe in approximately all studies. Pentoxifylline established its ability to shorten the healing time of this type of mouth ulcers. However, its potential to prevent the recurrence of the disease could not established based the data presented here. In conclusion, this systematic review suggests pentoxifylline in RAS patients because it confirmed that RAS patients who received this agent as oral administration reported suitable response. However, conducting more clinical trials with larger sample size and long follow-up time especially to efficiently judge about its ability to the recurrence prevention still is necessary to develop clinical practice guidelines for management of RAS. https://jpc.tums.ac.ir/index.php/jpc/article/view/487