Purpose: Some studies report a role of leukotrienes in the pathogenesis of atopic dermatitis and suggest a rationale for the use of leukotriene receptor antagonist (LTRA) in the treatment of atopic dermatitis. This study aimed to evaluate the treatment effectiveness of montelukast in children with atopic dermatitis. Methods: Fifty-four children between the ages of 2 and 6 years with moderate to severe atopic dermatitis were enrolled. Group A received montelukast for 8 weeks, followed by a crossover to 8 weeks of placebo after a 2-week washout period. Group B reversed the administration according to a randomized, double-blind, placebo-controlled, crossover design. The SCORing atopic dermatitis (SCORAD) index, urinary leukotriene E-4 (LTE4), and eosinophil-derived neurotoxin (EDN) were assessed at every visit. Results: Forty-three patients (21 males) completed the study. Although the SCORAD index was decreased in both groups, there was no statistically significant difference between montelukast and placebo (-3.0+/-11.2 vs -5.7+/-11.3, P=0.43). The level of urinary LTE4 was decreased after taking montelukast when compared to placebo, but there was no statistically significant difference (-65.9+/-556.2 vs 87.7+/-618.3, P=0.26). The changes in urinary EDN after taking montelukast and placebo had no significant difference (37.0+/-1,008.6 vs -195.8+/-916.7, P=0.10). When analyzing SCORAD indices, urinary LTE4, and EDN, we could not prove the effectiveness of montelukast in the atopic, non-atopic or high ECP (ECP >= 15 mu g/L) subgroups. Conclusions: There was no statistically significant difference in clinical improvement or biomarkers between montelukast and placebo treatment. Therefore, conventional treatments with skin care and infection control might be more important strategies in the treatment of atopic dermatitis.