Diaper dermatitis is a common cutaneous disorder in neonates and infants, which is caused by chemical irritants, maceration, zinc deficiency and microorganisms. This study aimed to compare the therapeutic effects of three commercial products (Nystatin, Clotrimazole and Mupirocin) in infants suffering from diaper dermititis. This singlecenter, randomized controlled study was carried out in Iran. A total of 112 infants were included in this trial and assigned to 3 experimental groups (Clotrimazole, Nystatin and Mupirocin) and 1 control group (zinc oxide). Survey participants underwent a designed treatment programs for 7 days. Total symptom score after 7 days (TSS-7) and beginning of recovery were assessed as efficacy parameters. All statistical analyses were conducted using Statistical Package for Social Sciences (SPSS), version 19. Although the severity of diaper dermatitis was significantly decreased in all groups by the end of trial (P <0.001), the reduction rate was found to be considerably greater in the Clotrimazole (2.54±0.58 to 0.75±0.65) and Mupirocin (2.17±0.71 to 1.00±0.91), respectively. In addition, time required for first response was significantly lower in Mupirocin, in comparison with the other medications. Clotrimazole and Mupirocin were superior to others with respect to reduction of symptom score and time of recovery, respectively. Therefore, it is important to determine the etiology of skin distruption and priorities of treatment to apply the best therapeutical approach.