Background: Topical corticosteroids are currently used for treatment of diaper dermatitis. Previous studies have shown the efficacy of sucralfate in the treatment of diaper dermatitis and contact dermatitis in peri-stomy areas. Objectives: To evaluate the efficacy of topical sucralfate in comparison with hydrocortisone cream in the treatment of diaper dermatitis. Patients and Methods: In a double-blind, randomized clinical trial, 64 patients with diaper dermatitis were treated with sucralfate cream 4% or hydrocortisone cream. The duration of treatment was 8 weeks and patients were evaluated every two weeks until complete healing. The results were evaluated with chi-square test. Results: Complete healing (More than 50% improvement) occurred in 90.6% and partial healing (20-50% improvement) in 9.4% of patients in each group (P>0.05). Conclusion: Topical sucralfate is an effective, available and cheap therapeutic intervention for diaper dermatitis, which has equal efficacy with topical hydrocortisone cream.