Background: Diaper rash is a common but non life threateningcondition during infancy. Different modalities of treatmentare suggested. Sucralfate acts as a physical barrier to irritantsand has antibacterial activities. Promising reports of the effectof topical sucralfate on wound epithelialization along with itsbacteriostatic properties led us to carry out a trial to evaluateits role as a topical agent in the treatment of diaper dermatitisand compare its efficacy with topical zinc oxide.Method: This double blind randomized clinical trial was conductedin Shariati hospital from April 2008 to September 2009. Sucralfateand zinc oxide were formulated as 20% ointments with the sameexcipients. All patients were randomly treated topically witheither sucralfate (N=25) or zinc oxide (N=21) for 7 days. Diaperseverity scores were obtained before treatment and at days 3, 5,7 by the authors.Result: A total of 46 infants (54.3% female and 45.7% male) withmean age of 4.4±6.5 months entered the study. The mean age,sex, frequency of diaper change (per day) and severity of diaperrash showed no statistically significant difference between twogroups. Sucralfate 20% ointment was significantly superior inhealing diaper dermatitis at days 5 and 7 (p < 0.05 and 0.01respectively) and showed a significantly shorter healing time(3.24+/-2.02 days) in comparison with zinc oxide 20% ointment(5.42+/-2.39 days) (P = 0.002).Conclusion: Since sucralfate in topical formulations acts as aphysical barrier with proved safety and no noticeable absorption,it may be used as a potential treatment for diaper dermatitis.